PIM3

Summary

PIM3 (Pim-3 proto-oncogene, serine/threonine kinase, HGNC:19310) is a protein-coding gene on chromosome 22q13.33, encoding Serine/threonine-protein kinase pim-3 (Q86V86). Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation.

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is overexpressed in hematological and epithelial tumors and is associated with MYC coexpression. It plays a role in the regulation of signal transduction cascades, contributing to both cell proliferation and survival, and provides a selective advantage in tumorigenesis.

Source: NCBI Gene 415116 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 45 total
• Druggable target: yes — 24 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001001852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19310
Approved symbol	PIM3
Name	Pim-3 proto-oncogene, serine/threonine kinase
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198355
Ensembl biotype	protein_coding
OMIM	610580
Entrez	415116

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000360612, ENST00000467480, ENST00000897645, ENST00000897646, ENST00000933528, ENST00000933529, ENST00000933530, ENST00000933531, ENST00000966144

RefSeq mRNA: 1 — MANE Select: NM_001001852 NM_001001852

CCDS: CCDS33678

Canonical transcript exons

ENST00000360612 — 6 exons

Exon	Start	End
ENSE00001408637	49962689	49962865
ENSE00001409228	49961442	49961811
ENSE00001413115	49961125	49961234
ENSE00001415895	49960772	49961032
ENSE00001486858	49962940	49964072
ENSE00003481245	49961318	49961368

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.8933 / max 1655.9485, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192946	55.2241	1812
192947	3.4863	934
192949	3.2707	889
209528	2.4469	1212
192950	1.4653	367

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.44	gold quality
skin of abdomen	UBERON:0001416	97.27	gold quality
skin of leg	UBERON:0001511	97.24	gold quality
zone of skin	UBERON:0000014	97.01	gold quality
body of stomach	UBERON:0001161	97.00	gold quality
upper lobe of left lung	UBERON:0008952	96.77	gold quality
minor salivary gland	UBERON:0001830	96.53	gold quality
metanephros cortex	UBERON:0010533	96.51	gold quality
left uterine tube	UBERON:0001303	96.26	gold quality
saliva-secreting gland	UBERON:0001044	96.23	gold quality
omental fat pad	UBERON:0010414	96.23	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.17	gold quality
right lung	UBERON:0002167	96.13	gold quality
adipose tissue	UBERON:0001013	96.10	gold quality
gastrocnemius	UBERON:0001388	95.95	gold quality
blood	UBERON:0000178	95.66	gold quality
spleen	UBERON:0002106	95.65	gold quality
cortex of kidney	UBERON:0001225	95.51	gold quality
prostate gland	UBERON:0002367	95.35	gold quality
vagina	UBERON:0000996	95.33	gold quality
lower esophagus mucosa	UBERON:0035834	95.28	gold quality
apex of heart	UBERON:0002098	95.20	gold quality
endocervix	UBERON:0000458	95.19	gold quality
thoracic mammary gland	UBERON:0005200	95.14	gold quality
fundus of stomach	UBERON:0001160	95.07	gold quality
esophagus mucosa	UBERON:0002469	94.81	gold quality
adult mammalian kidney	UBERON:0000082	94.78	gold quality
muscle of leg	UBERON:0001383	94.69	gold quality
monocyte	CL:0000576	94.57	gold quality
stomach	UBERON:0000945	94.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.55
E-CURD-112	yes	11.51
E-MTAB-8271	no	522.74
E-GEOD-110499	no	202.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, ETV7, STAT3

miRNA regulators (miRDB)

42 targeting PIM3, 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-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4520-3P	98.75	66.55	963

Literature-anchored findings (GeneRIF, showing 40)

• Aberrnntly expressed Pim-3 can cause autonomous cell proliferation or prevent apoptosis in hepatoma cell lines. (PMID:15540201)
• Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels. (PMID:18593906)
• Ets-1 can induce aberrant Pim-3 expression and subsequently prevent apoptosis in human pancreatic cancer cells. (PMID:19154409)
• expression of Pim-1 & Pim-3 is induced in response reactivation in KSHV-infected cells; they are required for KSHV reactivation under these conditions; data indicate Pim-1 & Pim-3 contribute to viral reactivation by phosphorylating the KSHV LANA (PMID:19266083)
• Ginsenoside Rg3 decreased both Pim-3 and pBad expressions in a dose-dependent manner in PANC-1 cells. (PMID:19624871)
• Pim-3 alone cannot cause, but can accelerate HCC development. (PMID:20101231)
• A cell-based test system useful for rapid and inexpensive pre-screening of compounds capable of preventing Pim-mediated phosphorylation is discussed. (PMID:20939820)
• Pim-3 has an important role in modulating c-Myc and PGC-1alpha protein levels and cell growth (PMID:21187426)
• Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas. (PMID:21646687)
• Pim protein kinase-3 is regulated by TNF-alpha and promotes endothelial cell sprouting. (PMID:21870113)
• Our study indicates that the expression of Pim kinases is physiologically related to DNA-PKcs and ATM in ECs. (PMID:22282239)
• PIM kinases promote the production of IFNgamma, the hallmark cytokine produced by Th1 cells. (PMID:23209281)
• Pim-1 and Pim-3 play overlapping but non-identical roles as it relates to gemcitabine sensitivity of pancreatic cancer cells and Pim-3 is upregulated in pancreatic ductal carcinoma. (PMID:23760491)
• Pim-3 can promote pancreatic tumor growth and angiogenesis by stimulating the VEGF pathway. (PMID:23845873)
• observations indicate that TCTP enhances Pim-3 stability to simultaneously promote and prevent cell-cycle progression and apoptosis, respectively (PMID:24165482)
• the existence of different patterns of expression of Pim-3, c-Myc, and p-p27 and their clinicopathologic correlations in adenocarcinomas of the gastric cardia and the distal stomach. (PMID:24488669)
• we constructed a dual-function small hairpin RNA (shRNA) vector containing an shRNA targeting Pim-3 and a TLR7-stimulating ssRNA. (PMID:24723452)
• cancer development and in promoting tumor neovascularization and subsequent tumor growth. Targeting Pim-3 may play a dual role in halting tumor progression, by promoting tumor cell death and blocking angiogenesis (PMID:24789328)
• Blocking the activities of PIM kinases(PIM1, PIM2 and PIM3) could prevent pancreatic cancer development. PIM kinases(PIM1, PIM2 and PIM3) may be a novel target for cancer therapy (PMID:24799066)
• Data demonstrate the role of PIM kinases in driving myeloid leukemia, and as candidate molecules for therapy against human malignancies. (PMID:25238262)
• Knockdown of Pim-3 by specific shRNA slowed decreased proliferation, induced cell cycle arrest in the G0/G1 phase, and increased apoptosis in glioblastoma cells. (PMID:25817345)
• PIM3 expression is higher in ovarian cancer than in normal ovarian tissue. Upregulation of PIM3 promotes proliferation and migration of ovarian cancer cells. (PMID:25921139)
• Pim-3 kinase enhances growth and metastatic properties of prostate cancer xenografts. PC-3 prostate cancer cells overexpressing either Pim-1 or Pim-3 kinases form larger xenograft tumors than the parental PC-3 cells. (PMID:26075720)
• MicroRNA506 participates in pancreatic cancer pathogenesis by targeting PIM3 (PMID:26238203)
• A high percentage of urothelial carcinomas express Pim kinases. Pim expression differs in NILG, NIHG, and IHG lesions. (PMID:26551340)
• Pim-3 expression showed a positive correlation with tumor cell differentiation. (PMID:26768612)
• Pim-3 has a role in human pancreatic cancer cell survival against radiation (PMID:27016481)
• show that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. (PMID:27448973)
• SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of nasopharyngeal carcinoma cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel. (PMID:27525970)
• Pim-3 expression was inversely correlated with that of miR-377. (PMID:27638830)
• The expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. (PMID:27826135)
• Our study suggests that up-regulation of Pim-3 successfully accelerated Chronic Obstructive Pulmonary Disease development, and aggravated lung damage (PMID:28214201)
• PIM kinases in classical Hodgkin lymphoma exhibit pleiotropic effects, orchestrating tumor immune escape and supporting Reed-Sternberg cell survival. (PMID:28698206)
• These results demonstrate the involvement of PIM kinases in LIF-induced regulation in different trophoblastic cell lines which may indicate similar functions in primary cells. (PMID:28729093)
• results demonstrate that PIM3 is induced upon mTORC1 inhibition, with potential implications for the effects of mTORC1 inhibitors in TSC, cancers, and the many other disease settings influenced by aberrant mTORC1 signaling. (PMID:29170467)
• Study identified that PIM1 and PIM3 phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1 and revealed a regulatory mechanism of virus-host interaction that governs viral escape from an intrinsic cellular immune defense via the post-translational modification of viral protein. (PMID:31015445)
• The down-regulation of Pim-3 was closely related to the activation status of the lung STAT3 signaling pathway, mediated cell proliferation inhibition and induced apoptosis. (PMID:31882428)
• Proto-Oncogene Serine/Threonine Kinase PIM3 Promotes Cell Migration via Modulating Rho GTPase Signaling. (PMID:31994402)
• High Expression of NEK2 and PIM1, but Not PIM3, Is Linked to an Aggressive Phenotype of Bronchopulmonary Neuroendocrine Neoplasms. (PMID:32504181)
• Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. (PMID:32707033)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pim3	ENSDARG00000055129
mus_musculus	Pim3	ENSMUSG00000035828
rattus_norvegicus	Pim3	ENSRNOG00000029698

Paralogs (2): PIM2 (ENSG00000102096), PIM1 (ENSG00000137193)

Protein

Protein identifiers

Serine/threonine-protein kinase pim-3 — Q86V86 (reviewed: Q86V86)

All UniProt accessions (1): Q86V86

UniProt curated annotations — full annotation on UniProt →

Function. Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.

Subunit / interactions. Interacts with BAD. Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM3, ubiquitination and proteasomal degradation. Interacts with SOCS6.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in various tissues, including the heart, brain, lung, kidney, spleen, placenta, skeletal muscle, and peripheral blood leukocytes. Not found or barely expressed in the normal adult endoderm-derived organs such as colon, thymus, liver, or small intestine. However, expression is augmented in premalignant and malignant lesions of these organs.

Post-translational modifications. Ubiquitinated, leading to proteasomal degradation. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.

RefSeq proteins (1): NP_001001852* (*=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
IPR017348	PIM1/2/3	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR051138	PIM_Ser/Thr_kinase	Family

Pfam: PF00069

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 (7 total): binding site 2, sequence conflict 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V86-F1	85.64	0.78

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): 170 (proton acceptor)

Ligand- & substrate-binding residues (2): 46–54; 69

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_RESPONSE_TO_KETONE

GO Biological Process (6): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of mitotic cell cycle (GO:0007346), negative regulation of apoptotic process (GO:0043066), negative regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061179), cellular response to forskolin (GO:1904322)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), 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 (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitotic cell cycle	1
regulation of cell cycle	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
insulin secretion involved in cellular response to glucose stimulus	1
negative regulation of insulin secretion	1
negative regulation of response to stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
cellular response to lipid	1
cellular response to alcohol	1
cellular response to ketone	1
response to forskolin	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1531 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIM3	SHANK3	Q9BYB0	671
PIM3	ALG12	Q9BV10	585
PIM3	BCL2L1	Q07817	578
PIM3	RABL2B	Q9UNT1	572
PIM3	HASPIN	Q8TF76	562
PIM3	RABL2A	Q9UBK7	552
PIM3	IL2	P01585	520
PIM3	EWSR1	Q01844	509
PIM3	SMARCB1	Q12824	495
PIM3	APPL2	Q8NEU8	429
PIM3	MYC	P01106	419
PIM3	TIFAB	Q6ZNK6	419
PIM3	DAPK2	Q9UIK4	408
PIM3	PIM2	Q9P1W9	404
PIM3	COPS7B	Q9H9Q2	394

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PIM3	MDM2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
HSP90AB1	PIM3	psi-mi:“MI:0915”(physical association)	0.400
PIM3	MYO1C	psi-mi:“MI:0914”(association)	0.350
PIM1	IDH3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): PIM3 (Positive Genetic), PIM3 (Affinity Capture-RNA), MYO1C (Affinity Capture-MS), ARPC1B (Affinity Capture-MS), ARPC3 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), MYO1B (Affinity Capture-MS), HNRNPCL1 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), WDR1 (Affinity Capture-MS), FLOT1 (Affinity Capture-MS), MYO1D (Affinity Capture-MS), LMNA (Affinity Capture-MS), TP53 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RPR8, D3ZGQ5, O09127, O19179, O54784, O70444, O75676, O88764, O95382, P05128, P05129, P06803, P0DPD7, P0DPE0, P10829, P11309, P26794, P51840, P52785, P54760, P55203, P58750, P63318, P63319, P97343, Q02846, Q3U3Q1, Q4R4U2, Q5JZY3, Q5QNM6, Q5RCY1, Q5Z6X0, Q62070, Q63285, Q6ERS4, Q6PHR2, Q86SG6, Q86V86, Q8C1R0, Q8TAS1

Diamond homologs: A0AUV4, A1A5Q6, B2DD29, B7XHR6, C0HKC8, C0HKC9, D3ZML2, F1QGZ6, O08679, O22932, O22971, O54863, O59697, O60285, O70444, O94168, P06803, P11309, P26794, P31374, P52497, P54645, P57059, P58750, P92958, Q00372, Q00771, Q05512, Q08217, Q0JI49, Q13131, Q14680, Q19469, Q1PFH8, Q20443, Q28GW8, Q38997, Q54DF2, Q54MV2, Q54WX4

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SGI-1776	down-regulates	PIM3	“chemical inhibition”
PIM3	“down-regulates activity”	BAD	phosphorylation
PIM3	“up-regulates quantity”	CXCR4	phosphorylation
PIM3	“up-regulates activity”	PSMD2	phosphorylation
PIM3	“up-regulates activity”	NFATC1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

632 predictions. Top by Δscore:

Variant	Effect	Δscore
22:49961028:GCCAG:G	donor_gain	1.0000
22:49961033:G:GG	donor_gain	1.0000
22:49961033:GT:G	donor_loss	1.0000
22:49961123:A:AG	acceptor_gain	1.0000
22:49961124:G:GG	acceptor_gain	1.0000
22:49961124:GCC:G	acceptor_gain	1.0000
22:49961124:GCCAA:G	acceptor_gain	1.0000
22:49961235:G:GG	donor_gain	1.0000
22:49961235:G:T	donor_loss	1.0000
22:49961236:TGA:T	donor_loss	1.0000
22:49961237:GA:G	donor_loss	1.0000
22:49961313:CGCAG:C	acceptor_loss	1.0000
22:49961314:GCAGG:G	acceptor_loss	1.0000
22:49961315:CAGGT:C	acceptor_loss	1.0000
22:49961317:G:GA	acceptor_loss	1.0000
22:49961364:GCCTG:G	donor_gain	1.0000
22:49961808:GACG:G	donor_gain	1.0000
22:49961809:ACG:A	donor_gain	1.0000
22:49961809:ACGG:A	donor_loss	1.0000
22:49961810:CGGT:C	donor_loss	1.0000
22:49961811:GGT:G	donor_loss	1.0000
22:49961812:G:C	donor_loss	1.0000
22:49961812:G:GG	donor_gain	1.0000
22:49961813:T:A	donor_loss	1.0000
22:49962684:CTTA:C	acceptor_loss	1.0000
22:49962685:TTA:T	acceptor_loss	1.0000
22:49962686:TA:T	acceptor_loss	1.0000
22:49962687:A:AG	acceptor_gain	1.0000
22:49962688:G:GG	acceptor_gain	1.0000
22:49962852:G:GT	donor_gain	1.0000

AlphaMissense

2091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:49961190:T:C	F51L	1.000
22:49961192:C:A	F51L	1.000
22:49961192:C:G	F51L	1.000
22:49961327:A:G	K69E	1.000
22:49961329:G:C	K69N	1.000
22:49961329:G:T	K69N	1.000
22:49961592:T:C	F133L	1.000
22:49961594:C:A	F133L	1.000
22:49961594:C:G	F133L	1.000
22:49961701:G:C	R169P	1.000
22:49961703:G:C	D170H	1.000
22:49961704:A:C	D170A	1.000
22:49961704:A:G	D170G	1.000
22:49961704:A:T	D170V	1.000
22:49961705:C:A	D170E	1.000
22:49961705:C:G	D170E	1.000
22:49961709:A:C	K172Q	1.000
22:49961709:A:G	K172E	1.000
22:49961710:A:T	K172M	1.000
22:49961711:G:C	K172N	1.000
22:49961711:G:T	K172N	1.000
22:49961716:A:T	E174V	1.000
22:49961718:A:C	N175H	1.000
22:49961718:A:G	N175D	1.000
22:49961719:A:C	N175T	1.000
22:49961719:A:G	N175S	1.000
22:49961720:T:A	N175K	1.000
22:49961720:T:G	N175K	1.000
22:49961760:G:C	D189H	1.000
22:49961761:A:C	D189A	1.000

dbSNP variants (sampled 300 via entrez): RS1000043387 (22:49959059 C>T), RS1000152175 (22:49961946 G>A), RS1000371618 (22:49961789 C>A,G,T), RS1000392516 (22:49962300 T>G), RS1000467771 (22:49962627 C>G,T), RS1000706067 (22:49962505 G>A,T), RS1001275679 (22:49964462 C>T), RS1001510223 (22:49958855 C>G,T), RS1001783474 (22:49959536 C>G), RS1001835896 (22:49959740 G>A), RS1002194121 (22:49963208 C>T), RS1002252386 (22:49958990 C>A,T), RS1002411572 (22:49963043 C>T), RS1002999711 (22:49959996 A>C,G), RS1003634228 (22:49963912 G>T)

Disease associations

OMIM: gene MIM:610580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000861_8	Cannabis dependence	8.000000e-06
GCST000964_30	Ulcerative colitis	2.000000e-07
GCST002481_12	Acne (severe)	4.000000e-06
GCST004133_55	Ulcerative colitis	2.000000e-10
GCST007515_13	Type 2 diabetes	2.000000e-07
GCST007516_35	Type 2 diabetes (adjusted for BMI)	4.000000e-08
GCST007517_28	Type 2 diabetes	7.000000e-06
GCST008362_75	Birth weight	1.000000e-08
GCST009379_307	Type 2 diabetes	2.000000e-08
GCST009379_308	Type 2 diabetes	1.000000e-06
GCST010118_83	Type 2 diabetes	2.000000e-17
GCST010241_366	Apolipoprotein A1 levels	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3559682 (PROTEIN FAMILY), CHEMBL5407 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

24 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 304,061 (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
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL960	LEFLUNOMIDE	4	52,218
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL1967878	CENISERTIB	2	358
CHEMBL362558	LY-2090314	2	108
CHEMBL3975308	NUVISERTIB	2	100
CHEMBL4467168	DAPOLSERTIB	2	22
CHEMBL475251	R-406	2	762
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1952329	SGI-1776	1	400
CHEMBL1969664	AZD-1080	1
CHEMBL269538	HARMINE	1
CHEMBL3651966	LGH-447	1
CHEMBL494089	GSK-690693	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — PIM family

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
LGB321	Inhibition	12.1	pKi
PIM447	Inhibition	11.05	pKi
GDC-0339	Inhibition	10.7	pKi
uzansertib	Inhibition	9.92	pIC50
AZD1208	Inhibition	9.64	pKi
CX-6258	Inhibition	7.8	pIC50
nuvisertib	Inhibition	7.38	pKi
SGI-1776	Inhibition	7.16	pIC50
compound 14k [PMID: 21982499]	Inhibition	7.07	pIC50
compound 20 [PMID: 22136433]	Inhibition	7.05	pIC50
compound 1a [PMID: 24900749]	Inhibition	6.82	pIC50

Binding affinities (BindingDB)

882 measured of 1565 human assays (1565 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-amino-N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	IC50	0.01 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.01 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(oxan-4-yl)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.01 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(4-fluorooxan-4-yl)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.01 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.01 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
5-[1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]pyrazolo[4,3-c]pyridin-6-yl]-3-methylpyrazin-2-amine	KI	0.012 nM	US-9434725: 5-azaindazole compounds and methods of use
(3S)-1-[3-cyclopropyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridinyl]piperidin-3-amine	KI	0.014 nM	US-9434725: 5-azaindazole compounds and methods of use
(3S)-1-[3-methyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridinyl]piperidin-3-amine	KI	0.018 nM	US-9434725: 5-azaindazole compounds and methods of use
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-methylsulfanylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(3R,4S,5S)-3-amino-5-methyl-4-(1,2,4-triazol-1-yl)piperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]-N-methylcarbamate	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-propan-2-ylphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-propan-2-yloxyphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(4-hydroxyoxan-4-yl)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
5-amino-N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4R,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4R,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(1-hydroxycyclobutyl)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4R,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-propan-2-yloxyphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4R,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-propan-2-yloxyphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
3-amino-N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(2-methylsulfonylethoxy)cyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[6-(2,6-difluoro-4-propan-2-yloxyphenyl)-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]carbamate	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[6-[2,6-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]carbamate	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(3R,4S,5S)-3-amino-5-methyl-4-(triazol-1-yl)piperidin-1-yl]-3-pyridinyl]-6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-methoxyphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
3-amino-N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(triazol-1-yl)cyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(oxan-4-yloxy)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[3-amino-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]carbamate	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
3-amino-N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(triazol-1-yl)cyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-4-(2-cyanoethoxy)-5-methylcyclohexyl]-3-pyridinyl]-6-[2,6-difluoro-4-(1-hydroxycyclobutyl)phenyl]-5-fluoropyridine-2-carboxamide	IC50	0.02 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
6-[6-(azetidin-1-yl)pyrazin-2-yl]-1-(6-piperazin-1-yl-2-pyridinyl)pyrazolo[4,3-c]pyridine	KI	0.02 nM	US-9434725: 5-azaindazole compounds and methods of use
1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine	KI	0.0204 nM	US-9434725: 5-azaindazole compounds and methods of use
1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-6-(6-ethylpyrazin-2-yl)pyrazolo[4,3-c]pyridine	KI	0.021 nM	US-9434725: 5-azaindazole compounds and methods of use
(3S)-1-[3-methoxy-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridinyl]piperidin-3-amine	KI	0.0212 nM	US-9434725: 5-azaindazole compounds and methods of use
6-[1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]pyrazolo[4,3-c]pyridin-6-yl]pyrazin-2-amine	KI	0.023 nM	US-9434725: 5-azaindazole compounds and methods of use
5-amino-N-[5-[(4R)-4-aminoazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.024 nM	US-8669361: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
(3S)-1-[3-cyclopropyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]pyrazin-2-yl]piperidin-3-amine	KI	0.026 nM	US-9434725: 5-azaindazole compounds and methods of use
2-[[6-[1-(6-piperazin-1-yl-2-pyridinyl)pyrazolo[4,3-c]pyridin-6-yl]pyrazin-2-yl]amino]ethanol	KI	0.026 nM	US-9434725: 5-azaindazole compounds and methods of use
5-amino-N-[5-(4-aminoazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.027 nM	US-8669361: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
6-methyl-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridinyl]piperidin-3-amine	KI	0.028 nM	US-9434725: 5-azaindazole compounds and methods of use
N-[4-[(3R,4S,5S)-3-amino-5-methyl-4-(triazol-1-yl)piperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4S,5S)-3-amino-5-methyl-4-(1,2,4-triazol-1-yl)cyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[6-(2,6-difluorophenyl)-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]-N-methylcarbamate	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(1R,3R,4R,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carboxamide	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
N-[4-[(3R,4S,5S)-3-amino-4-[4-(hydroxymethyl)triazol-1-yl]-5-methylpiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[5-amino-2-(2,6-difluorophenyl)-1,3-thiazole-4-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]carbamate	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
methyl N-[(3R,4S,5S)-3-amino-1-[3-[[6-(2,6-difluoro-4-methylphenyl)-5-fluoropyridine-2-carbonyl]amino]-4-pyridinyl]-5-methylpiperidin-4-yl]carbamate	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors
5-amino-N-[4-[(1R,3R,4S,5S)-3-amino-4-methoxy-5-methylcyclohexyl]-3-pyridinyl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	IC50	0.03 nM	US-8987457: Ring-substituted N-pyridinyl amides as kinase inhibitors

ChEMBL bioactivities

1925 potent at pChembl≥5 of 1943 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL3634781
11.00	Ki	0.01	nM	CHEMBL3634783
11.00	Ki	0.01	nM	CHEMBL3652638
11.00	Ki	0.01	nM	CHEMBL3623162
11.00	Ki	0.01	nM	CHEMBL4453890
11.00	Ki	0.01	nM	CHEMBL4439756
11.00	Ki	0.01	nM	CHEMBL4469964
10.96	Ki	0.011	nM	CHEMBL3906798
10.96	Ki	0.011	nM	CHEMBL3953164
10.89	Ki	0.013	nM	CHEMBL3634771
10.89	Ki	0.013	nM	CHEMBL3634767
10.89	Ki	0.013	nM	CHEMBL3914639
10.85	Ki	0.014	nM	CHEMBL3896312
10.85	Ki	0.014	nM	CHEMBL3982539
10.85	Ki	0.014	nM	CHEMBL3959091
10.82	Ki	0.015	nM	CHEMBL3634757
10.82	Ki	0.015	nM	CHEMBL3634758
10.80	Ki	0.016	nM	CHEMBL3634772
10.80	Ki	0.016	nM	CHEMBL3976267
10.77	Ki	0.017	nM	CHEMBL3634770
10.74	Ki	0.018	nM	CHEMBL3910536
10.72	Ki	0.019	nM	CHEMBL2387465
10.72	Ki	0.019	nM	CHEMBL3943705
10.72	Ki	0.019	nM	CHEMBL3932475
10.72	Ki	0.019	nM	CHEMBL3940744
10.70	Ki	0.0199	nM	CHEMBL3960554
10.70	Ki	0.02	nM	CHEMBL3898989
10.70	Ki	0.02	nM	CHEMBL3956349
10.70	Ki	0.02	nM	CHEMBL3634758
10.70	Ki	0.02	nM	CHEMBL3960554
10.70	Ki	0.02	nM	CHEMBL4076913
10.70	Ki	0.02	nM	CHEMBL3676285
10.70	Ki	0.02	nM	CHEMBL4449930
10.70	Ki	0.02	nM	CHEMBL3648680
10.70	Ki	0.02	nM	CHEMBL4459538
10.68	Ki	0.021	nM	CHEMBL3634756
10.68	Ki	0.021	nM	CHEMBL3946464
10.66	Ki	0.022	nM	CHEMBL2387463
10.66	Ki	0.022	nM	CHEMBL2387479
10.66	Ki	0.022	nM	CHEMBL2387471
10.66	Ki	0.022	nM	CHEMBL3652626
10.66	Ki	0.022	nM	CHEMBL3937096
10.64	Ki	0.023	nM	CHEMBL3900258
10.63	Ki	0.0235	nM	CHEMBL3926007
10.60	Ki	0.025	nM	CHEMBL2387474
10.60	Ki	0.025	nM	CHEMBL3927952
10.60	Ki	0.025	nM	CHEMBL3926007
10.60	Ki	0.025	nM	CHEMBL3951741
10.59	Ki	0.026	nM	CHEMBL3961692
10.59	Ki	0.026	nM	CHEMBL3983351

PubChem BioAssay actives

772 with measured affinity, of 2060 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
N-[2-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]phenyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	1692891: Inhibition of PIM3 (unknown origin)	ic50	<0.0001	uM
3-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-5-(1-methylpyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
5-amino-N-[5-(4-amino-5-fluorocycloheptyl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridazine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
5-amino-2-(2,6-difluorophenyl)-N-[1-methyl-5-[(4S)-4-(2,2,2-trifluoroethylamino)azepan-1-yl]pyrazol-4-yl]-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-amino-N-[5-[(4R,5S)-4-amino-5-hydroxyazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-amino-N-[5-[(4S)-4-(2,2-difluoroethylamino)azepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-amino-N-[5-[(3S,5R)-5-amino-3-methoxyazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
3-amino-N-[4-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)pyridine-2-carboxamide	1062191: Inhibition of PIM3 (unknown origin) using Biotin-AGAGRSRHSSYPAGT-OH as substrate after 2 hrs by AlphaScreen assay	ki	<0.0001	uM
5-amino-N-[4-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
(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	2198370: Inhibition of human PIM3 using RSRHSSYPAGT as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	<0.0001	uM
N-[4-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	1266533: Inhibition of PIM3 kinase (unknown origin) using Biotin-AGAGRSRHSSYPAGT-OH as substrate after 2 hrs by alphascreen assay	ki	<0.0001	uM
N-[4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	1062195: Inhibition of PIM3 (unknown origin)	ki	<0.0001	uM
5-amino-N-[5-[(4S)-4-aminoazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-amino-N-[5-(4-amino-3-fluoroazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
3-amino-N-[4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	1062195: Inhibition of PIM3 (unknown origin)	ki	<0.0001	uM
3-amino-N-[4-[(3R,4R)-3-amino-4-hydroxypiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)pyridine-2-carboxamide	1062195: Inhibition of PIM3 (unknown origin)	ki	<0.0001	uM
N-[4-[(3S,5R)-3-amino-5-methylpiperidin-1-yl]-3-pyridinyl]-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine	1325394: Inhibition of Pim3 (unknown origin)	ic50	<0.0001	uM
(3S)-1-[6-(5-pyridin-3-yl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-pyridinyl]piperidin-3-amine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
(3S)-1-[3-methyl-6-[5-(1-methylpyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-2-pyridinyl]piperidin-3-amine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
5-[1-(cyclopropylmethyl)pyrazol-4-yl]-3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
3-(6-piperazin-1-yl-2-pyridinyl)-5-pyridin-3-yl-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
5-(1-ethylpyrazol-4-yl)-3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
5-(1-methylpyrazol-4-yl)-3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
(3S)-1-[6-[5-(1-methylpyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-2-pyridinyl]piperidin-3-amine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
5-(5-methyl-3-pyridinyl)-3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
(3R)-1-[6-[5-(1-methylpyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-2-pyridinyl]piperidin-3-amine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
(3R)-1-[6-[5-(1-methylpyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl]-2-pyridinyl]pyrrolidin-3-amine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
3-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-5-(6-methylpyrazin-2-yl)-1H-pyrazolo[3,4-c]pyridine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
5-(6-methylpyrazin-2-yl)-3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
2-[4-[3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridin-5-yl]pyrazol-1-yl]acetonitrile	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
N-[5-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-[[(3R,4R)-3-fluoropiperidin-4-yl]methylamino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
5-amino-N-[5-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
N-[5-(2,6-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-(piperidin-4-ylmethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
N-[5-(2,6-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-(2-piperidin-4-ylethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
5-[(4-fluoropiperidin-4-yl)methylamino]-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
N-[5-(2-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-(piperidin-4-ylmethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
N-[5-(2,6-difluorophenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-5-[[(3R,4R)-3-fluoropiperidin-4-yl]methylamino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
5-[[(3S,4S)-3-fluoropiperidin-4-yl]methylamino]-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749895: Inhibition of PIM3 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
5-amino-N-[5-[(4R,5R)-4-amino-5-fluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-amino-N-[5-[(5R)-5-amino-3,3-difluoro-5-methylazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
(3S)-1-[3-methoxy-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridinyl]piperidin-3-amine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
5-amino-N-[5-(5-amino-3-fluoroazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
1-[6-[(3R)-4,4-difluoropiperidin-3-yl]-2-pyridinyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine	1483006: Inhibition of PIM3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
5-amino-N-[5-[(1R,4R,5R)-4-amino-8-oxabicyclo[3.2.1]octan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
3-(2-fluorophenyl)-5-[4-[(3R)-piperidin-3-yl]oxy-3-pyridinyl]-1H-pyrazolo[3,4-c]pyridine	1256223: Inhibition of Pim3 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	0.0001	uM
2-[[(3S)-3-hydroxypyrrolidin-1-yl]methyl]-8-thiophen-3-yl-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one	437533: Inhibition of human PIM3 by scintillation counting	ki	0.0001	uM
5-amino-N-[5-[(5R)-5-amino-4,4-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	0.0001	uM
3-amino-N-[4-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]-6-(2-fluorophenyl)pyridine-2-carboxamide	1520510: Inhibition of recombinant human PIM3 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Dronabinol	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression, affects expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
Glupearl 19S	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
NSC668394	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

450 unique, capped per target: 419 binding, 30 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3812019	Binding	Inhibition of Pim1/2 in human KMS-12-BM cells assessed as phosphorylation of full-length BAD protein at Ser-112 incubated for 110 mins by flow cytometric analysis in presence of 20% FBS	Discovery and Optimization of Macrocyclic Quinoxaline-pyrrolo-dihydropiperidinones as Potent Pim-1/2 Kinase Inhibitors. — ACS Med Chem Lett
CHEMBL1963764	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PIM3	PubChem BioAssay data set
CHEMBL5160046	Toxicity	Binding affinity to human PIM3	Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TD82	HAP1 PIM3 (-) 1	Cancer cell line	Male
CVCL_TD83	HAP1 PIM3 (-) 2	Cancer cell line	Male
CVCL_TD84	HAP1 PIM3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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