PDPK1

Summary

PDPK1 (3-phosphoinositide dependent protein kinase 1, HGNC:8816) is a protein-coding gene on chromosome 16p13.3, encoding 3-phosphoinositide-dependent protein kinase 1 (O15530). Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases.

Enables 3-phosphoinositide-dependent protein kinase activity; phospholipase activator activity; and phospholipase binding activity. Involved in several processes, including cell surface receptor signaling pathway; intracellular signaling cassette; and regulation of signal transduction. Acts upstream of or within intracellular signal transduction. Located in cell projection; cytosol; and plasma membrane. Implicated in prostate cancer. Biomarker of lung non-small cell carcinoma.

Source: NCBI Gene 5170 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total — 1 pathogenic
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8816
Approved symbol	PDPK1
Name	3-phosphoinositide dependent protein kinase 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PDK1
Ensembl gene	ENSG00000140992
Ensembl biotype	protein_coding
OMIM	605213
Entrez	5170

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 protein_coding, 6 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000268673, ENST00000342085, ENST00000389224, ENST00000441549, ENST00000460496, ENST00000461815, ENST00000462923, ENST00000464702, ENST00000471311, ENST00000474706, ENST00000478708, ENST00000491073, ENST00000492021, ENST00000561962, ENST00000566659, ENST00000569721, ENST00000570136, ENST00000894430, ENST00000894431, ENST00000894432, ENST00000957853, ENST00000957854, ENST00000957855

RefSeq mRNA: 3 — MANE Select: NM_002613 NM_001261816, NM_002613, NM_031268

CCDS: CCDS10472, CCDS10473, CCDS58411

Canonical transcript exons

ENST00000342085 — 14 exons

Exon	Start	End
ENSE00000946017	2586676	2586893
ENSE00000946018	2595793	2595850
ENSE00000946019	2597123	2597275
ENSE00001505218	2597651	2603188
ENSE00003461739	2538021	2538136
ENSE00003471169	2583412	2583585
ENSE00003475577	2557703	2557963
ENSE00003518139	2565553	2565697
ENSE00003536573	2561480	2561522
ENSE00003556996	2577425	2577500
ENSE00003566614	2581295	2581363
ENSE00003582018	2566356	2566453
ENSE00003589393	2581607	2581703
ENSE00003633799	2561771	2561908

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4343 / max 79.4095, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152252	11.6500	1800
152251	1.2372	880
152250	1.2088	790
152255	0.2641	107
152253	0.0742	31

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.89	gold quality
middle temporal gyrus	UBERON:0002771	96.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.82	gold quality
bronchial epithelial cell	CL:0002328	95.66	gold quality
parotid gland	UBERON:0001831	95.54	gold quality
esophagus squamous epithelium	UBERON:0006920	95.53	gold quality
caput epididymis	UBERON:0004358	95.34	gold quality
corpus epididymis	UBERON:0004359	95.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.82	gold quality
lateral globus pallidus	UBERON:0002476	94.57	gold quality
visceral pleura	UBERON:0002401	94.55	gold quality
entorhinal cortex	UBERON:0002728	94.47	gold quality
tibia	UBERON:0000979	94.31	gold quality
skin of hip	UBERON:0001554	94.20	gold quality
parietal pleura	UBERON:0002400	94.12	gold quality
postcentral gyrus	UBERON:0002581	94.12	gold quality
colonic mucosa	UBERON:0000317	94.05	gold quality
jejunal mucosa	UBERON:0000399	93.95	gold quality
parietal lobe	UBERON:0001872	93.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.77	gold quality
germinal epithelium of ovary	UBERON:0001304	93.73	gold quality
superior frontal gyrus	UBERON:0002661	93.60	gold quality
pleura	UBERON:0000977	93.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.34	gold quality
pons	UBERON:0000988	93.32	gold quality
primary visual cortex	UBERON:0002436	93.07	gold quality
cauda epididymis	UBERON:0004360	92.95	gold quality
nipple	UBERON:0002030	92.83	gold quality
mammary duct	UBERON:0001765	92.74	gold quality
upper leg skin	UBERON:0004262	92.60	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GDNF, JUN, PPARD

miRNA regulators (miRDB)

235 targeting PDPK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670

Literature-anchored findings (GeneRIF, showing 40)

• PDPK1 activity is regulated by reversible phosphorylation, possibly by a member of the Src kinase family. (PMID:11481331)
• association of PDK1 with Hsp90 regulates its stability, solubility, and signaling (PMID:11779851)
• Substitution of the autophosphorylation site Thr516 with a negatively charged residue confers constitutive activity to mouse 3-phosphoinositide-dependent protein kinase-1 in cells (PMID:11877406)
• Data show that the translocation of 3-phosphoinositide-dependent protein kinase-1 from cytosol to the plasma membrane is critical for Akt and glycogen synthase kinase-3 activation. (PMID:12147684)
• A point mutation in the substrate-binding region of PDK1 (L155E) rendered PDK1 incapable of phosphorylating PKB. (PMID:12167717)
• 2.0 A crystal structure of the PDK1 kinase domain in complex with ATP (PMID:12169624)
• 14-3-3 protein binds to PDK1 at Ser241 and negatively regulates PDK1 kinase activity. (PMID:12177059)
• PDK1 kinase activity is negatively regulated by binding to 14-3-3 (PMID:12177059)
• In some growth factor-activated AGC protein kinases, phosphorylation of the hydrophobic motif creates a specific docking site that recruits and activates PDK1, which then phosphorylates the activation loop. (PMID:12374740)
• PDK1 has a role in activating atypical PKC and regulating the degradation of p21(WAF1) (PMID:12485998)
• The in vivo role of the PIF-binding site of PDK1 is defined by knock-in mutation. (PMID:12912918)
• peroxisomal targeting signal (PTS)-tagged CISK with deleted PX domain was able to direct 3-phosphoinositide-dependent protein kinase-1 (PDK-1) into peroxisomes (PMID:14604990)
• Src- & ROS-dependent PDK1 activation leads to site-specific PAK1 phosphorylation. This is critically important for PDGF-induced VSMC migration, a process integral to the vascular response to injury that leads to vessel occlusion & plaque formation. (PMID:15059930)
• role in metabolic actions of insulin (PMID:15210700)
• the integrity of the alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop phosphorylation (PMID:15741170)
• PDK1 undergoes rapid and transient phosphorylation on S396, which was dependent upon plasma membrane localization; phosphorylation of S396 is necessary for nuclear shuttling of PDK1. (PMID:15743829)
• PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells (PMID:15802604)
• results indicate that 3-phosphoinositide-dependent protein kinase-1 is a critical regulator of cell survival by modulating the IkappaB kinase (IKK)/nuclear factor-kappaB pathway (PMID:16207722)
• STRAP acts as an intermediate signaling molecule linking between the phosphatidylinositol 3-kinase/PDK1 and the TGF-beta signaling pathways (PMID:16251192)
• PDK-1 may promote oncogenesis in part through the activation of AKT and p7 (PMID:16288304)
• PDK1 mediates mammary epithelial cell growth and invasion in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen (PMID:16551362)
• PDK1-catalyzed trans-phosphorylation of PDK1-Tide approximates a Rapid Equilibrium Random Bi Bi system, where motions in the central ternary complex are largely rate-determining (PMID:16737971)
• These data reveals for the first time that PDK1 and PKB may differentially activate NF-kappaB, and that TPCK may subserve a useful anti-inflammatory function by inhibiting IKKbeta. (PMID:17136479)
• Ras is able to promote monocyte lineage selection via PKC and PDK1. (PMID:17255356)
• PDK1 negatively regulates TGF-beta-mediated signaling in a PDK1 kinase-dependent manner via a direct physical interaction with Smad proteins, and Smad proteins can act as potential positive regulators of PDK1 (PMID:17327236)
• Loss of PTEN expression in Jurkat T cells does not impact on the PDK-1/PKC pathway and that only a subset of kinases, such as PKB/Akt, are perturbed as a consequence PTEN loss. (PMID:17826953)
• PDK-1/AKT pathway is activated in RMS and may play an important role in survival of RMS(rhabdomyosarcoma). PDK-1/AKT pathway may be an attractive therapeutic target for cancer intervention in RMS using OSU-03012. (PMID:17848913)
• 3-Hydroxyanthranilic acid inhibits NF-kappaB activation upon T cell antigen receptor engagement by specifically targeting PDK1 (PMID:18003900)
• These data suggest that phosphorylation of PDK1 on Tyr(9), distinct from Tyr(373/376), is important for PDK1/Src complex formation, leading to PDK1 activation. (PMID:18024423)
• There is a non-catalytic role for PDK1 in regulating cortical acto-myosin and cell motility. (PMID:18204440)
• 7-ketocholesterol-induced apoptosis has a role in phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway (PMID:18495460)
• p21(Ras)-mediated survival signaling is regulated by via a PI(3)K-AKT pathway, which is dependent upon both PDK1 and PKCdelta, and PDK1 activates and regulates PKCdelta to determine the fate of cells containing a mutated, activated p21(Ras). (PMID:19146951)
• Our findings suggest that IGF-I may regulate neuronal PDK-1 differently than in non-neuronal cells, which may indicate a novel role for PDK-1 in IGF-I-mediated neuroprotective signaling. (PMID:19276999)
• The SHP-1:PDK1 complex between the cytoplasm and the nucleus is dependent on a specific sequence of events; initial recruitment of PDK1 to perinuclear PIPs, followed by SHP-1 mediated entry via the nuclear pore complex and PDK-1 mediated nuclear export. (PMID:19591923)
• The identification of c-Jun as a transcriptional regulator of PDK1 expression highlights key mechanisms underlying c-Jun oncogenic activity, and provides new insight into the nature of up-regulated Akt and PKC in melanoma. (PMID:19910471)
• results provide evidence that PDK1 and ASK1 directly interact and phosphorylate each other and act as negative regulators of their respective kinases in resting cells (PMID:19920149)
• disruption of phosphoinositide-dependent kinase-1 interaction with IGF-1R reduces IGF-1 survival effects in cancer cells (PMID:20044479)
• Data show that AKT1 and AKT2 appeared to regulate growth through FOXO proteins, but not through either GSK3beta or mTOR, and in contrast, inactivation of PDPK1 affected GSK3beta and mTOR activation. (PMID:20133737)
• We evaluated the presence of mutations in PIK3CA, AKT1, AKT2, AKT3, PTEN, and PDPK1 genes in 83 papillary thyroid carcinomas (PMID:20186503)
• These studies show that PDK1 plays a pivotal role in MAPK and PI3K signaling in tumor cells. (PMID:20197379)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdpk1b	ENSDARG00000018285
danio_rerio	pdpk1a	ENSDARG00000062304
mus_musculus	Pdpk1	ENSMUSG00000024122
rattus_norvegicus	Pdpk1	ENSRNOG00000006136
drosophila_melanogaster	Pdk1	FBGN0020386
caenorhabditis_elegans		WBGENE00003965

Paralogs (5): PRKCQ (ENSG00000065675), AKT2 (ENSG00000105221), AKT3 (ENSG00000117020), AKT1 (ENSG00000142208), PRKCD (ENSG00000163932)

Protein

Protein identifiers

3-phosphoinositide-dependent protein kinase 1 — O15530 (reviewed: O15530)

All UniProt accessions (7): O15530, E9PER6, H3BNV5, H3BPR5, H3BPW1, H3BQ10, H3BQA3

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), TSSK3, protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Catalytically inactive.

Subunit / interactions. Homodimer in its autoinhibited state. Active as monomer. Interacts with NPRL2, PPARG, PAK1, PTK2B, GRB14, PKN1 (via C-terminus), STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 and CRK (via their SH2 domains). Interacts with SGK3 in a phosphorylation-dependent manner. The tyrosine-phosphorylated form interacts with PTPN6. The Ser-241 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7. Interacts with PKN2; the interaction stimulates PDPK1 autophosphorylation, its PI(3,4,5)P3-dependent kinase activity toward ‘Ser-473’ of AKT1 but also activates its kinase activity toward PRKCD and PRKCZ.

Subcellular location. Cytoplasm. Nucleus. Cell membrane. Cell junction. Focal adhesion.

Tissue specificity. Appears to be expressed ubiquitously. The Tyr-9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast.

Post-translational modifications. Phosphorylation on Ser-241 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-241, leading to its own activation. Autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. Tyr-9 phosphorylation is critical for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-241 and palmitate-induced phosphorylation at Ser-529 and Ser-501 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-354 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-394 and Ser-398 by MAP3K5. Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. Monoubiquitinated in the kinase domain, deubiquitinated by USP4.

Activity regulation. Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-241 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin.

Domain organisation. The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization. The PIF-pocket is a small lobe in the catalytic domain required by the enzyme for the binding to the hydrophobic motif of its substrates. It is an allosteric regulatory site that can accommodate small compounds acting as allosteric inhibitors.

Induction. Stimulated by insulin, and the oxidants hydrogen peroxide and peroxovanadate.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
O15530-1	1	yes
O15530-2	2
O15530-3	3
O15530-4	4
O15530-5	5

RefSeq proteins (3): NP_001248745, NP_002604, NP_112558 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR033931	PDK1-typ_PH	Domain
IPR039046	PDPK1	Family
IPR050236	Ser_Thr_kinase_AGC	Family

Pfam: PF00069, PF14593

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (91 total): helix 21, strand 18, modified residue 15, mutagenesis site 14, binding site 6, turn 6, splice variant 4, domain 2, region of interest 2, chain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

70 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5LVO	X-RAY DIFFRACTION	1.09
5ACK	X-RAY DIFFRACTION	1.24
4CT2	X-RAY DIFFRACTION	1.25
5LVM	X-RAY DIFFRACTION	1.26
8DQT	X-RAY DIFFRACTION	1.31
5LVN	X-RAY DIFFRACTION	1.38
4XX9	X-RAY DIFFRACTION	1.4
5LVL	X-RAY DIFFRACTION	1.4
5MRD	X-RAY DIFFRACTION	1.41
4RRV	X-RAY DIFFRACTION	1.41
4AW0	X-RAY DIFFRACTION	1.43
1W1G	X-RAY DIFFRACTION	1.45
1W1H	X-RAY DIFFRACTION	1.45
1W1D	X-RAY DIFFRACTION	1.5
4RQV	X-RAY DIFFRACTION	1.5
4RQK	X-RAY DIFFRACTION	1.55
4AW1	X-RAY DIFFRACTION	1.68
1UU3	X-RAY DIFFRACTION	1.7
3RCJ	X-RAY DIFFRACTION	1.7
3NAX	X-RAY DIFFRACTION	1.75
2VKI	X-RAY DIFFRACTION	1.8
3QC4	X-RAY DIFFRACTION	1.8
4A07	X-RAY DIFFRACTION	1.85
4CT1	X-RAY DIFFRACTION	1.85
1UU7	X-RAY DIFFRACTION	1.9
3HRF	X-RAY DIFFRACTION	1.9
3HRC	X-RAY DIFFRACTION	1.91
3RWP	X-RAY DIFFRACTION	1.92
1UU9	X-RAY DIFFRACTION	1.95
2BIY	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15530-F1	80.24	0.58

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 205 (proton acceptor)

Ligand- & substrate-binding residues (6): 166; 209; 223; 92–94; 111; 160–162

Post-translational modifications (15): 9, 25, 241, 304, 354, 373, 376, 393, 394, 396, 398, 410, 501, 513, 529

Mutagenesis-validated functional residues (14):

Position	Phenotype
9	slight reduction in pervanadate-stimulated tyrosine phosphorylation.
25	no effect.
241	no activation.
277	3-fold increase in kinase activity.
354	abolishes phosphorylation by melk.
373	reduction in basal activity.
376	reduction in basal activity.
393	no effect.
394	abolishes phosphorylation by map3k5; when associated with a-398.
396	no effect.
398	abolishes phosphorylation by map3k5; when associated with a-394.
410	no effect.
474	no pdgf-dependent translocation to the membrane.
513	enhanced kinase activity towards pkb.

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-165158	Activation of AKT2
R-HSA-202424	Downstream TCR signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-354192	Integrin signaling
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-444257	RSK activation
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-9634635	Estrogen-stimulated signaling through PRKCZ
R-HSA-9735871	SARS-CoV-1 targets host intracellular signalling and regulatory pathways
R-HSA-9755779	SARS-CoV-2 targets host intracellular signalling and regulatory pathways
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells

MSigDB gene sets: 891 (showing top): PID_BCR_5PATHWAY, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, BIOCARTA_PTEN_PATHWAY, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_EPITHELIAL_CELL_DEVELOPMENT, REACTOME_PLATELET_AGGREGATION_PLUG_FORMATION, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION

GO Biological Process (33): type B pancreatic cell development (GO:0003323), protein phosphorylation (GO:0006468), hyperosmotic response (GO:0006972), epidermal growth factor receptor signaling pathway (GO:0007173), insulin receptor signaling pathway (GO:0008286), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), cell migration (GO:0016477), calcium-mediated signaling (GO:0019722), actin cytoskeleton organization (GO:0030036), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), T cell costimulation (GO:0031295), cellular response to insulin stimulus (GO:0032869), negative regulation of toll-like receptor signaling pathway (GO:0034122), intracellular signal transduction (GO:0035556), regulation of canonical NF-kappaB signal transduction (GO:0043122), regulation of mast cell degranulation (GO:0043304), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of angiogenesis (GO:0045766), protein autophosphorylation (GO:0046777), insulin-like growth factor receptor signaling pathway (GO:0048009), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to epidermal growth factor stimulus (GO:0071364), extrinsic apoptotic signaling pathway (GO:0097191), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), intracellular signaling cassette (GO:0141124), positive regulation of protein localization to plasma membrane (GO:1903078), positive regulation of sprouting angiogenesis (GO:1903672), positive regulation of vascular endothelial cell proliferation (GO:1905564), negative regulation of endothelial cell apoptotic process (GO:2000352), regulation of endothelial cell migration (GO:0010594), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), 3-phosphoinositide-dependent protein kinase activity (GO:0004676), ATP binding (GO:0005524), phospholipase activator activity (GO:0016004), phospholipase binding (GO:0043274), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), postsynaptic density (GO:0014069), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), ciliary tip (GO:0097542), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Fc epsilon receptor (FCERI) signaling	2
VEGFA-VEGFR2 Pathway	2
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
PI3K Cascade	1
TCR signaling	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Co-stimulation by CD28	1
G-protein beta:gamma signalling	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
C-type lectin receptors (CLRs)	1
RHO GTPase Effectors	1
PI3K/AKT Signaling in Cancer	1
Regulation of TP53 Expression and Degradation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular signaling cassette	2
intracellular anatomical structure	2
protein kinase activity	2
cytoplasm	2
epithelial cell development	1
type B pancreatic cell differentiation	1
phosphorylation	1
protein modification process	1
response to osmotic stress	1
ERBB signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
regulation of toll-like receptor signaling pathway	1
signal transduction	1
canonical NF-kappaB signal transduction	1
regulation of intracellular signal transduction	1
regulation of myeloid leukocyte mediated immunity	1
regulation of leukocyte degranulation	1
mast cell degranulation	1
positive regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
angiogenesis	1

Protein interactions and networks

STRING

2468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDPK1	AKT1	P31749	927
PDPK1	PTEN	P60484	848
PDPK1	RICTOR	Q6R327	805
PDPK1	PIK3CA	P42336	744
PDPK1	TSC2	P49815	736
PDPK1	PIK3CB	P42338	706
PDPK1	MTOR	P42345	696
PDPK1	HSP90AA1	P07900	691
PDPK1	IRS1	P35568	688
PDPK1	FOXO1	Q12778	684
PDPK1	HSP90AB1	P08238	679
PDPK1	PIK3CG	P48736	672
PDPK1	SRC	P12931	670
PDPK1	MAPKAP1	Q9BPZ7	655
PDPK1	AKTIP	Q9H8T0	650

IntAct

100 interactions, top by confidence:

A	B	Type	Score
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
PDPK1	AKT1	psi-mi:“MI:0217”(phosphorylation reaction)	0.820
PDPK1	AKT1	psi-mi:“MI:0915”(physical association)	0.820
PDPK1	AKT1	psi-mi:“MI:2364”(proximity)	0.820
AKT1	PDPK1	psi-mi:“MI:2364”(proximity)	0.820
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
PDPK1	TBL2	psi-mi:“MI:0915”(physical association)	0.620
YWHAH	PDPK1	psi-mi:“MI:0915”(physical association)	0.560
PDPK1	YWHAQ	psi-mi:“MI:0915”(physical association)	0.540
PDPK1	YWHAQ	psi-mi:“MI:0407”(direct interaction)	0.540
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
PDPK1	PDPK1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
PDPK1	HSPA8	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
PPP2R2B	PDPK1	psi-mi:“MI:0915”(physical association)	0.520
PDPK1	PPP2R2B	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (302): PDPK1 (Biochemical Activity), PDPK1 (Two-hybrid), PDPK1 (Affinity Capture-Western), PDPK1 (Affinity Capture-MS), TBL2 (Affinity Capture-MS), SERPINA4 (Affinity Capture-MS), CPA4 (Affinity Capture-MS), FAM199X (Affinity Capture-MS), PRKCZ (Two-hybrid), PDPK1 (Two-hybrid), PDPK1 (Two-hybrid), PDPK1 (Affinity Capture-MS), PDPK1 (Affinity Capture-MS), PDPK1 (Affinity Capture-MS), PDPK1 (Co-localization)

ESM2 similar proteins: A2VDU3, A8WFU8, B2DD29, D4A7V9, F1QGZ6, O08796, O15530, O35280, O43318, O54785, O54992, P0C8E4, P32866, P42331, P53351, P53666, P53668, P53669, P53670, P53671, P62205, P70531, Q00944, Q14680, Q28GW8, Q32L23, Q38997, Q5R4L1, Q5RFL3, Q5RJI5, Q61083, Q61084, Q61846, Q62073, Q69Z98, Q6DD21, Q6DE87, Q6P549, Q8BYW1, Q8IWQ3

Diamond homologs: A0A078CGE6, A0QNG1, A5TY84, A5TY85, A5U3A3, A5U3A6, A6QGC0, B0BBT2, B3NE99, B4PDM5, O15530, O22971, O34507, O55173, P0A5S5, P0DPS8, P0DPS9, P33973, P49695, P51957, P54736, P54738, P54739, P54740, P54741, P54742, P54743, P54744, P65727, P65731, P65733, P9WI62, P9WI63, P9WI64, P9WI65, P9WI66, P9WI67, P9WI68, P9WI69, P9WI70

SIGNOR signaling

99 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	PDPK1	phosphorylation
PDPK1	up-regulates	PRKCE	phosphorylation
PDPK1	up-regulates	MAP2K2	phosphorylation
PDPK1	up-regulates	PRKCA	phosphorylation
PDPK1	up-regulates	PRKCB	phosphorylation
PDPK1	up-regulates	PRKCG	phosphorylation
PDPK1	up-regulates	RPS6KB2	phosphorylation
PDPK1	up-regulates	SGK2	phosphorylation
PDPK1	up-regulates	SGK3	phosphorylation
PDPK1	“up-regulates activity”	AKT2	phosphorylation
PDPK1	up-regulates	CARD11	phosphorylation
PDPK1	up-regulates	PRKCQ	phosphorylation
PDPK1	up-regulates	RPS6KA3	phosphorylation
IGF1R	up-regulates	PDPK1	phosphorylation
SRC	up-regulates	PDPK1	phosphorylation
PHT-427	down-regulates	PDPK1	“chemical inhibition”
PIP3	“up-regulates activity”	PDPK1	relocalization
PDPK1	up-regulates	AKT1	phosphorylation
PDPK1	up-regulates	RPS6KB1	phosphorylation
N-[3-[[5-bromo-4-[2-(1H-imidazol-5-yl)ethylamino]-2-pyrimidinyl]amino]phenyl]-1-pyrrolidinecarboxamide	down-regulates	PDPK1	“chemical inhibition”
OSU-03012	down-regulates	PDPK1	“chemical inhibition”
PDPK1	unknown	PDPK1	phosphorylation
PDPK1	“up-regulates activity”	MAP2K1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Deactivation of the beta-catenin transactivating complex	5	17.9×	1e-03
TP53 Regulates Metabolic Genes	5	10.0×	4e-03
Metabolism of vitamins and cofactors	5	9.0×	5e-03
SARS-CoV-2 Infection	7	8.7×	1e-03
SARS-CoV Infections	9	7.7×	6e-04
Viral Infection Pathways	10	4.7×	3e-03
Infectious disease	12	4.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	6	16.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

47 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	34
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564254	GRCh37/hg19 16p13.3-13.13(chr16:85880-11209288)x3	Pathogenic

SpliceAI

3335 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2557701:A:AG	acceptor_gain	1.0000
16:2557702:G:GG	acceptor_gain	1.0000
16:2557702:GT:G	acceptor_gain	1.0000
16:2557702:GTAT:G	acceptor_gain	1.0000
16:2557963:GGTG:G	donor_loss	1.0000
16:2557965:T:A	donor_loss	1.0000
16:2561519:GCGA:G	donor_gain	1.0000
16:2561521:GA:G	donor_gain	1.0000
16:2561523:G:GG	donor_gain	1.0000
16:2579470:A:T	donor_gain	1.0000
16:2583408:TAA:T	acceptor_loss	1.0000
16:2583409:AAG:A	acceptor_gain	1.0000
16:2583410:AGGTT:A	acceptor_loss	1.0000
16:2583581:GCAAT:G	donor_gain	1.0000
16:2583582:CAAT:C	donor_gain	1.0000
16:2583583:AAT:A	donor_gain	1.0000
16:2583585:TG:T	donor_loss	1.0000
16:2583586:G:GG	donor_gain	1.0000
16:2583587:T:G	donor_loss	1.0000
16:2586671:TGCA:T	acceptor_loss	1.0000
16:2586673:CAG:C	acceptor_loss	1.0000
16:2586674:A:AC	acceptor_loss	1.0000
16:2586674:A:AG	acceptor_gain	1.0000
16:2586674:AGTAT:A	acceptor_gain	1.0000
16:2586675:G:GC	acceptor_gain	1.0000
16:2586675:GT:G	acceptor_gain	1.0000
16:2586675:GTA:G	acceptor_gain	1.0000
16:2586675:GTAT:G	acceptor_gain	1.0000
16:2586675:GTATG:G	acceptor_gain	1.0000
16:2586890:CTTGG:C	donor_loss	1.0000

AlphaMissense

3630 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2557923:T:C	F82S	1.000
16:2557943:G:A	G89R	1.000
16:2557943:G:C	G89R	1.000
16:2557943:G:T	G89W	1.000
16:2557944:G:A	G89E	1.000
16:2557949:G:A	G91S	1.000
16:2557949:G:C	G91R	1.000
16:2557949:G:T	G91C	1.000
16:2557950:G:A	G91D	1.000
16:2557955:T:C	F93L	1.000
16:2557957:T:A	F93L	1.000
16:2557957:T:G	F93L	1.000
16:2557958:T:C	S94P	1.000
16:2557959:C:A	S94Y	1.000
16:2557959:C:T	S94F	1.000
16:2561481:T:A	V96D	1.000
16:2561520:C:A	A109E	1.000
16:2561773:A:C	K111Q	1.000
16:2561773:A:G	K111E	1.000
16:2561774:A:T	K111I	1.000
16:2561775:A:C	K111N	1.000
16:2561775:A:T	K111N	1.000
16:2561780:T:C	L113P	1.000
16:2561785:A:G	K115E	1.000
16:2561787:G:C	K115N	1.000
16:2561787:G:T	K115N	1.000
16:2561811:G:C	K123N	1.000
16:2561811:G:T	K123N	1.000
16:2561870:T:A	V143D	1.000
16:2561887:T:C	F149L	1.000

dbSNP variants (sampled 300 via entrez): RS1000079769 (16:2551968 G>C), RS1000101989 (16:2537368 C>A,T), RS1000133086 (16:2537129 T>C), RS1000166053 (16:2541284 C>G), RS1000232434 (16:2601522 C>G,T), RS1000266217 (16:2586386 G>A), RS1000283424 (16:2546028 A>G), RS1000397786 (16:2545771 C>T), RS1000419612 (16:2588302 A>C), RS1000504179 (16:2598158 T>G), RS1000543203 (16:2557511 G>A), RS1000587670 (16:2585049 G>C), RS1000656579 (16:2578963 T>C), RS1000689319 (16:2584914 C>T), RS1000716690 (16:2578022 C>T)

Disease associations

OMIM: gene MIM:605213 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_366	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2534 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 240,100 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1980297	ILORASERTIB	2	581
CHEMBL253896	XANTHOHUMOL	2	2,525
CHEMBL362558	LY-2090314	2	108
CHEMBL475251	R-406	2	762
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1084546	PF-00562271	1	399
CHEMBL1650595	AR-12	1	713
CHEMBL1908397	KW-2449	1	622
CHEMBL1980391	RG-1530	1
CHEMBL259084	MLN-8054	1
CHEMBL482967	CYC-116	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — PDK1 family

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
GSK2334470	Inhibition	8.6	pIC50
OSU-03012	Inhibition	8.05	pIC50
BX-795	Inhibition	7.96	pIC50
BX-912	Inhibition	7.59	pIC50
7-hydroxystaurosporine	Inhibition	7.48	pIC50
compound 1 [PMID: 20005102]	Inhibition	7.3	pIC50
PHT-427	Inhibition	5.28	pKi

Binding affinities (BindingDB)

872 measured of 1761 human assays (1762 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(1R)-1-(3,4-difluorophenyl)-2-hydroxyethyl]-N-[3-[3-[(1-ethylpiperidin-4-yl)amino]quinoxalin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-[3-[(1-methylpiperidin-4-yl)amino]quinolin-6-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	1 nM	US-8575203: Chemical compounds
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-N-[3-[3-[(1-ethylpiperidin-4-yl)amino]quinolin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-(3H-imidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3-fluorophenyl)-2-hydroxyethyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
2-[(3,4-difluorophenyl)methyl]-6-methoxy-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-3-oxopyridazine-4-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-N-[3-[1-[4-(dimethylamino)cyclohexyl]-2-methylimidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
6-chloro-2-[(3,4-difluorophenyl)methyl]-N-[3-[1-(1-methylpiperidin-4-yl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-3-oxopyridazine-4-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
N-[3-[1-[4-(dimethylamino)cyclohexyl]imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-1-[(1R)-1-(3-fluorophenyl)-2-hydroxyethyl]-2-oxopyridine-3-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-(1-ethylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	1 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
Jak Inhibitor 1	EC50	1 nM
PDK1 inhibitor, 7	EC50	1 nM
Staurosporine	KD	1.7 nM
1-[(1R)-1-(3,4-difluorophenyl)ethyl]-N-[3-[3-[(1-methylpiperidin-4-yl)amino]quinoxalin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-[3-[(4-morpholin-4-ylcyclohexyl)amino]quinoxalin-6-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-N-[3-[3-[(1-ethylpiperidin-4-yl)amino]quinoxalin-6-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[3-[[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]amino]quinoxalin-6-yl]prop-2-ynyl]-1-[(1S)-1-(3-fluorophenyl)-2-hydroxyethyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[3-[[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]amino]quinoxalin-6-yl]prop-2-ynyl]-2-[(3,4-difluorophenyl)methyl]-3-oxopyridazine-4-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-[3-[(1-ethylpiperidin-4-yl)amino]quinolin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[3-[(1-ethylpiperidin-4-yl)amino]quinolin-6-yl]prop-2-ynyl]-1-[(1S)-1-(3-fluorophenyl)-2-hydroxyethyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-6-oxo-N-[3-[4-(piperidin-3-ylmethoxy)quinolin-6-yl]prop-2-ynyl]pyrimidine-5-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[1-(3,4-difluorophenyl)ethyl]-N-[3-[4-[3-(dimethylamino)propoxy]quinolin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[1-(3,4-difluorophenyl)-2-hydroxyethyl]-N-[3-[4-[3-(dimethylamino)propoxy]quinolin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[4-[[(3S)-1-methylpyrrolidin-3-yl]methoxy]quinolin-6-yl]prop-2-ynyl]-2-oxo-1-[(3,4,5-trifluorophenyl)methyl]pyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[4-[[(3R)-1-methylpiperidin-3-yl]methoxy]quinolin-6-yl]prop-2-ynyl]-2-oxo-1-[(3,4,5-trifluorophenyl)methyl]pyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
N-[3-[4-[[(3R)-1-methylpiperidin-3-yl]methoxy]quinolin-6-yl]prop-2-ynyl]-2-oxo-1-[1-(3,4,5-trifluorophenyl)ethyl]pyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[2-hydroxy-1-(3,4,5-trifluorophenyl)ethyl]-N-[3-[4-[[(3R)-1-methylpiperidin-3-yl]methoxy]quinolin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-[1-(3-hydroxypropyl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-[1-(1-methylpiperidin-4-yl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
2-[(1R)-1-(3,4-difluorophenyl)ethyl]-6-methyl-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-3-oxopyridazine-4-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3,4-difluorophenyl)-2-hydroxyethyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1R)-2-hydroxy-1-phenylethyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1R)-2-amino-1-(3,4-difluorophenyl)ethyl]-N-[3-(2-methyl-1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-2-oxo-N-[3-[1-(1-propan-2-ylpiperidin-4-yl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]pyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(1S)-1-(3,4-difluorophenyl)ethyl]-N-[3-[2-methyl-1-(1-methylpiperidin-4-yl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-[2-methyl-1-(oxan-3-yl)imidazo[4,5-c]quinolin-8-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-6-oxo-N-[3-(1-propan-2-ylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]pyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
1-[(3,4-difluorophenyl)methyl]-N-[3-(1-ethyl-2-methylimidazo[4,5-c]quinolin-8-yl)prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	2 nM	US-8895581: 1H-imidazo[4,5-c]quinolines
2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide	IC50	2.3 nM
2-(N-[2-amino-6-[5-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrimidin-4-yl]-2-chloroanilino)ethanol	IC50	2.6 nM	US-9238651: 1-H-pyrrolo[2,3-b]pyridine derivatives
1-[(3,4-difluorophenyl)methyl]-6-oxo-N-[3-[3-(piperidin-4-ylamino)quinoxalin-6-yl]prop-2-ynyl]pyrimidine-5-carboxamide	IC50	3 nM	US-8575203: Chemical compounds
N-[3-[3-[(4-aminocyclohexyl)amino]quinoxalin-6-yl]prop-2-ynyl]-1-[(3,4-difluorophenyl)methyl]-6-oxopyrimidine-5-carboxamide	IC50	3 nM	US-8575203: Chemical compounds
1-[(1R)-1-(3,4-difluorophenyl)-2-hydroxyethyl]-N-[3-[3-[(1-methylpiperidin-4-yl)amino]quinoxalin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	3 nM	US-8575203: Chemical compounds
N-[3-[3-[[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]amino]quinoxalin-6-yl]prop-2-ynyl]-1-[(3,4-difluorophenyl)methyl]-6-oxopyrimidine-5-carboxamide	IC50	3 nM	US-8575203: Chemical compounds
1-[(1R)-1-(3,4-difluorophenyl)-2-hydroxyethyl]-N-[3-[3-[[1-(2-methoxyethyl)piperidin-4-yl]amino]quinoxalin-6-yl]prop-2-ynyl]-2-oxopyridine-3-carboxamide	IC50	3 nM	US-8575203: Chemical compounds
1-[(3,4-difluorophenyl)methyl]-N-[3-[3-[[1-(oxetan-3-yl)piperidin-4-yl]amino]quinoxalin-6-yl]prop-2-ynyl]-6-oxopyrimidine-5-carboxamide	IC50	3 nM	US-8575203: Chemical compounds

ChEMBL bioactivities

1317 potent at pChembl≥5 of 1476 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.26	IC50	0.556	nM	STAUROSPORINE
9.22	Ki	0.6	nM	CHEMBL1940246
9.22	Ki	0.6	nM	CHEMBL1938415
9.20	IC50	0.631	nM	CHEMBL1765751
9.15	Ki	0.7	nM	CHEMBL1940251
9.10	IC50	0.7943	nM	CHEMBL1765750
9.05	Ki	0.9	nM	CHEMBL1940247
9.00	IC50	1	nM	CHEMBL3689220
9.00	IC50	1	nM	CHEMBL3689239
9.00	IC50	1	nM	CHEMBL3689244
9.00	IC50	1	nM	CHEMBL3644680
9.00	IC50	1	nM	CHEMBL3644700
9.00	IC50	1	nM	CHEMBL3644710
9.00	IC50	1	nM	CHEMBL3644712
9.00	IC50	1	nM	CHEMBL3644732
9.00	IC50	1	nM	CHEMBL3644741
9.00	IC50	1	nM	CHEMBL3644750
9.00	IC50	1	nM	CHEMBL3644753
9.00	IC50	1	nM	CHEMBL3644758
9.00	EC50	1	nM	CHEMBL1234429
9.00	Ki	1	nM	CHEMBL1940250
8.90	Ki	1.259	nM	CHEMBL1980995
8.89	Ki	1.3	nM	CHEMBL1940248
8.85	Ki	1.4	nM	CHEMBL1940252
8.85	Ki	1.4	nM	CHEMBL1940253
8.80	IC50	1.585	nM	CHEMBL1765738
8.80	Ki	1.585	nM	CHEMBL592030
8.77	Kd	1.7	nM	STAUROSPORINE
8.70	IC50	2	nM	CHEMBL3689201
8.70	IC50	2	nM	CHEMBL3689210
8.70	IC50	2	nM	CHEMBL3689221
8.70	IC50	2	nM	CHEMBL3689231
8.70	IC50	2	nM	CHEMBL3689232
8.70	IC50	2	nM	CHEMBL3689241
8.70	IC50	2	nM	CHEMBL3689245
8.70	IC50	2	nM	CHEMBL3689292
8.70	IC50	2	nM	CHEMBL3689293
8.70	IC50	2	nM	CHEMBL3689294
8.70	IC50	2	nM	CHEMBL3689303
8.70	IC50	2	nM	CHEMBL3689310
8.70	IC50	2	nM	CHEMBL3689311
8.70	IC50	2	nM	CHEMBL3689314
8.70	IC50	2	nM	CHEMBL3644683
8.70	IC50	2	nM	CHEMBL3644689
8.70	IC50	2	nM	CHEMBL3644695
8.70	IC50	2	nM	CHEMBL3644697
8.70	IC50	2	nM	CHEMBL3644703
8.70	IC50	2	nM	CHEMBL3644704
8.70	IC50	2	nM	CHEMBL3644713
8.70	IC50	2	nM	CHEMBL3644722

PubChem BioAssay actives

539 with measured affinity, of 2895 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	2198364: Inhibition of human PDK1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0006	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(3S,4R)-4-(4-fluorophenyl)oxolan-3-yl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0006	uM
N-[(3R,5R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-5-methylpiperidin-3-yl]-N,3,3-trimethylbutanamide	592178: Inhibition of PDK1	ic50	0.0006	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(1R,2R)-2-(4-fluorophenyl)cyclopentyl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0006	uM
(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-(4-fluorophenyl)pyrrolidine-1-carbaldehyde	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0007	uM
tert-butyl N-[(3R,5R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-5-methylpiperidin-3-yl]-N-methylcarbamate	592178: Inhibition of PDK1	ic50	0.0008	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(1R,2R)-2-(4-fluorophenyl)cyclopentyl]-methylamino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0009	uM
1-[(3,4-difluorophenyl)methyl]-2-oxo-N-[(1R)-2-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)oxy]-1-phenylethyl]pyridine-3-carboxamide	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ec50	0.0010	uM
4-tert-butyl-15-fluoro-3,5,10-triazatetracyclo[11.4.0.02,6.07,12]heptadeca-1(13),2(6),4,7(12),8,14,16-heptaen-11-one	1799765: Proliferation Assay from Article 10.1074/jbc.M110.156463: “Genetic and pharmacological inhibition of PDK1 in cancer cells: characterization of a selective allosteric kinase inhibitor.”	ec50	0.0010	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(2R,3R)-2-(4-fluorophenyl)pyrrolidin-3-yl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0010	uM
1-[(3,4-difluorophenyl)methyl]-2-oxo-N-[2-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)oxy]-1-phenylethyl]pyridine-3-carboxamide	1799765: Proliferation Assay from Article 10.1074/jbc.M110.156463: “Genetic and pharmacological inhibition of PDK1 in cancer cells: characterization of a selective allosteric kinase inhibitor.”	ec50	0.0010	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(2R,3R)-2-(4-fluorophenyl)oxolan-3-yl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0013	uM
1-[(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-phenylpyrrolidin-1-yl]ethanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0014	uM
1-[(2R,3R)-3-[[6-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidine-5-carbonyl)pyrazin-2-yl]amino]-2-(4-fluorophenyl)pyrrolidin-1-yl]ethanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0014	uM
(3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-6-methyl-N-phenylpiperidine-3-carboxamide	592178: Inhibition of PDK1	ic50	0.0016	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(1R,2R)-2-phenylcyclopentyl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0020	uM
N-[3-[[5-bromo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	729483: Displacement of [gamma33P]ATP from human TBK1 expressed in insect sf21 cells measured for 30 mins	ic50	0.0023	uM
(3S,6R)-1-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-N-cyclohexyl-6-methylpiperidine-3-carboxamide	1310405: Inhibition of PDK1 (unknown origin)	ic50	0.0025	uM
(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-[6-[[(3S,4S)-4-(4-fluorophenyl)pyrrolidin-3-yl]amino]pyrazin-2-yl]methanone	641893: Inhibition of recombinant human His-tagged PDK1 catalytic domain using Ac-Sox-PKTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIAD-NH2 as substrate by fluorescence-based spectrophotometry	ki	0.0025	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]-3-piperidin-1-ylpropanamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0030	uM
[(3Z)-2-oxo-3-[1-(1H-pyrrol-2-yl)propylidene]-1H-indol-5-yl]urea	1797577: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.04.071: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity.”	ic50	0.0030	uM
[(3Z)-3-[[4-[3-(aminomethyl)phenyl]-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indol-5-yl]urea	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0030	uM
2-[5-[(2R)-2-aminopropoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0030	uM
2-[5-[(2R)-2-aminobutoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0030	uM
2-[5-[(2S)-2-amino-3-(4-fluorophenyl)propoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0030	uM
(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-6-methyl-N-phenylpiperidine-3-carboxamide	592178: Inhibition of PDK1	ic50	0.0032	uM
(2S,5R)-4-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-5-ethyl-N-phenylmorpholine-2-carboxamide	592178: Inhibition of PDK1	ic50	0.0032	uM
(2S,5R)-4-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-N-cyclohexyl-5-methylmorpholine-2-carboxamide	592178: Inhibition of PDK1	ic50	0.0032	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507667: Binding affinity to PDPK1	kd	0.0034	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]-1-methylpiperidine-4-carboxamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0040	uM
3-[5-[(Z)-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]methyl]-1H-pyrrol-3-yl]-N-[2-(dimethylamino)ethyl]benzamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0040	uM
3-[5-[(Z)-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]methyl]-1H-pyrrol-3-yl]-N-(2-piperidin-1-ylethyl)benzamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0040	uM
[(3Z)-2-oxo-3-[1-(1H-pyrrol-2-yl)ethylidene]-1H-indol-5-yl]urea	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0050	uM
2-amino-N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]acetamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0050	uM
3-[5-[(Z)-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]methyl]-1H-pyrrol-3-yl]benzamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0050	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]pyridine-4-carboxamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0050	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]piperazine-2-carboxamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0050	uM
2-[5-(2-aminoethoxy)-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0050	uM
(2S,5R)-4-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-5-methyl-N-phenylmorpholine-2-carboxamide	592178: Inhibition of PDK1	ic50	0.0050	uM
(2S,3R,4R,6R,18R)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1797581: PDK1 Kinase Activity Assay from Article 10.1042/BJ20031119: “Structural basis for UCN-01 (7-hydroxystaurosporine) specificity and PDK1 (3-phosphoinositide-dependent protein kinase-1) inhibition.”	ic50	0.0050	uM
N-[3-[[5-iodo-4-[3-(thiophene-2-carbonylamino)propylamino]pyrimidin-2-yl]amino]phenyl]pyrrolidine-1-carboxamide	1797580: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1074/jbc.M501367200: “Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.”	ic50	0.0060	uM
N-[[5-[(1Z)-1-[5-(carbamoylamino)-2-oxo-1H-indol-3-ylidene]ethyl]-1H-pyrrol-3-yl]methyl]piperidine-4-carboxamide	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0060	uM
[(3Z)-3-[[4-(3-hydroxyphenyl)-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indol-5-yl]urea	1797575: PDK1-mediated AKT2 Activation Assay (cAKT2 33P-SPA) from Article 10.1016/j.bmcl.2007.05.060: “Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.”	ic50	0.0060	uM
2-[5-[(2S)-2-aminopropoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0060	uM
2-[5-[(2S)-2-aminobutoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0060	uM
2-[5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0060	uM
2-[5-[(2S)-2-amino-3-(3,4-dichlorophenyl)propoxy]-3-pyridinyl]-8,9-dimethoxybenzo[f][2,7]naphthyridin-4-amine	477040: Inhibition of human GST-tagged-PDK1 expressed in HEK293 cells	ic50	0.0060	uM
tert-butyl N-[(3R,5R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-5-methylpiperidin-3-yl]carbamate	592178: Inhibition of PDK1	ic50	0.0063	uM
(2S,5R)-4-[6-(3-amino-1H-indazol-6-yl)-2-(methylamino)pyrimidin-4-yl]-N-cyclohexyl-5-ethylmorpholine-2-carboxamide	592178: Inhibition of PDK1	ic50	0.0063	uM
(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)pyrimidin-4-yl]-N-cyclohexyl-6-methylpiperidine-3-carboxamide	592178: Inhibition of PDK1	ic50	0.0079	uM

CTD chemical–gene interactions

68 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases methylation, affects reaction, affects binding, increases reaction (+1 more)	3
Celecoxib	affects cotreatment, decreases expression, decreases phosphorylation, decreases activity	3
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
ON 01910	decreases phosphorylation	2
Acrolein	increases oxidation, increases abundance, affects cotreatment	2
Air Pollutants	increases oxidation, affects expression, affects cotreatment, increases abundance	2
Asbestos, Crocidolite	decreases expression, decreases phosphorylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
4’-methoxy-1-naphthylfenoterol	decreases expression	1
allyl isothiocyanate	decreases expression, decreases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
beryllium sulfate	decreases expression	1
maleic acid	decreases expression	1
bisdemethoxycurcumin	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
staurosporine aglycone	decreases activity	1
7-hydroxystaurosporine	decreases activity	1
cyanoginosin LR	increases phosphorylation	1
baohuoside I	decreases phosphorylation	1
Go 6976	decreases activity	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
OSU 03012	affects binding, decreases activity, decreases response to substance	1
OSU03013	decreases activity, affects binding	1
PF 5168899	affects localization, decreases reaction, decreases activity	1

ChEMBL screening assays

510 unique, capped per target: 502 binding, 7 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037985	Binding	Binding affinity to human PDPK1 at 200 nM by cell-based competition binding assay relative to control in presence of DTT	Staurosporine tethered peptide ligands that target cAMP-dependent protein kinase (PKA): optimization and selectivity profiling. — Bioorg Med Chem
CHEMBL1833068	Functional	Inhibition of PDK2 in human PC3 cells assessed as Akt Thr-308 dephosphorylation by Western blot analysis	Identification and characterization of a novel integrin-linked kinase inhibitor. — J Med Chem
CHEMBL4424900	ADMET	Inhibition of human N-terminal His6-tagged PDK1 (52 to end residues) expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8MB	Abcam HCT 116 PDPK1 KO	Cancer cell line	Male
CVCL_HD87	HCT 116 PDPK1(+/-)	Cancer cell line	Male
CVCL_JZ81	COMMA-1D/PDK1	Spontaneously immortalized cell line	Female
CVCL_TC86	HAP1 PDPK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.