PIM1

Summary

PIM1 (Pim-1 proto-oncogene, serine/threonine kinase, HGNC:8986) is a protein-coding gene on chromosome 6p21.2, encoding Serine/threonine-protein kinase pim-1 (P11309). Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. In precision oncology, PIM1 L2V is associated with resistance to Ibrutinib in Diffuse Large B-cell Lymphoma Activated B-cell Type (CIViC Level D); 2 further curated variant–drug associations are listed below.

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. It plays a role in signal transduction in blood cells, contributing to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Both the human and orthologous mouse genes have been reported to encode two isoforms (with preferential cellular localization) resulting from the use of alternative in-frame translation initiation codons, the upstream non-AUG (CUG) and downstream AUG codons (PMIDs:16186805, 1825810).

Source: NCBI Gene 5292 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total — 1 pathogenic
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_002648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8986
Approved symbol	PIM1
Name	Pim-1 proto-oncogene, serine/threonine kinase
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000137193
Ensembl biotype	protein_coding
OMIM	164960
Entrez	5292

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000373509, ENST00000468243, ENST00000479509, ENST00000897632, ENST00000897633, ENST00000933588, ENST00000943730, ENST00000943731

RefSeq mRNA: 2 — MANE Select: NM_002648 NM_001243186, NM_002648

CCDS: CCDS4830

Canonical transcript exons

ENST00000373509 — 6 exons

Exon	Start	End
ENSE00000750047	37170773	37170879
ENSE00000750048	37170981	37171031
ENSE00000750049	37171125	37171491
ENSE00001896529	37170152	37170657
ENSE00002087438	37173934	37175428
ENSE00003476312	37172996	37173172

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.7913 / max 2159.9173, expressed in 1804 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67604	39.3612	1761
67603	21.2559	1746
67607	1.9054	195
67605	0.8425	300
67606	0.7195	229
67608	0.4249	96
67609	0.1428	66
67610	0.1389	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.09	gold quality
left uterine tube	UBERON:0001303	97.85	gold quality
esophagus mucosa	UBERON:0002469	97.76	gold quality
granulocyte	CL:0000094	97.66	gold quality
mucosa of stomach	UBERON:0001199	97.23	gold quality
gall bladder	UBERON:0002110	97.08	gold quality
blood	UBERON:0000178	96.95	gold quality
skin of abdomen	UBERON:0001416	96.60	gold quality
skin of leg	UBERON:0001511	96.59	gold quality
tongue squamous epithelium	UBERON:0006919	96.15	gold quality
esophagus squamous epithelium	UBERON:0006920	96.14	gold quality
epithelium of esophagus	UBERON:0001976	95.54	gold quality
omental fat pad	UBERON:0010414	95.50	gold quality
peritoneum	UBERON:0002358	95.45	gold quality
ventricular zone	UBERON:0003053	95.41	gold quality
pharyngeal mucosa	UBERON:0000355	95.19	gold quality
buccal mucosa cell	CL:0002336	95.07	gold quality
leukocyte	CL:0000738	94.95	gold quality
monocyte	CL:0000576	94.81	gold quality
esophagus	UBERON:0001043	94.80	gold quality
mononuclear cell	CL:0000842	94.74	gold quality
vagina	UBERON:0000996	94.60	gold quality
bone marrow cell	CL:0002092	94.59	gold quality
zone of skin	UBERON:0000014	94.57	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.52	gold quality
bone marrow	UBERON:0002371	94.24	gold quality
smooth muscle tissue	UBERON:0001135	94.20	gold quality
vermiform appendix	UBERON:0001154	94.01	gold quality
mucosa of urinary bladder	UBERON:0001259	93.69	gold quality
vena cava	UBERON:0004087	93.68	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	155.37
E-CURD-112	yes	50.84
E-HCAD-4	yes	29.81
E-MTAB-9067	yes	11.26
E-MTAB-9388	yes	7.58
E-HCAD-9	yes	5.47
E-MTAB-9801	yes	5.35
E-MTAB-6678	yes	4.18
E-MTAB-10042	no	395.19
E-CURD-11	no	26.22
E-HCAD-10	no	2.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ABL1, AR, ERG, FLT3, HOXA9, KLF5, MYB, NR2C2, OLIG2, SP1, STAT1, STAT3, STAT4, STAT5A, STAT5B

miRNA regulators (miRDB)

114 targeting PIM1, 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-12118	100.00	65.88	1270
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 40)

• Upregulation by BCR/ABL requires activation of STAT5 and plays a key role in the BCR/ABL-mediated cell protection from apoptosis. (PMID:12036885)
• plays a role, most likely by phosphorylation, in promoting complex formation between NuMA, HP1beta, dynein and dynactin, a complex that is necessary for mitosis (PMID:12111331)
• The nuclear location of Pim-1 is essential for its regulation of the levels of HDM2 protein. (PMID:12680209)
• Overexpression of Pim-1 may attenuate androgen response during progression of prostate cancer in a cell context-dependent fashion. (PMID:13679438)
• Pim1 and Etk are required for IL6-induced activation of androgen receptor-mediated transcription in prostate cancer. (PMID:14981536)
• PIM-1 overexpression in high-grade prostatic intraepithelial neoplasia (HGPIN) may be an early event in prostate malignancy development; PIM-1 expression provides supplementary information for distinguishing HGPIN from benign epithelium. (PMID:15264249)
• Data show that the protein kinase Cdc25 C-associated kinase 1 (C-TAK1) is a binding partner and a substrate of Pim-1, and suggest a role for Pim-1 as a positive regulator at the G(2)/M transition of the cell cycle. (PMID:15319445)
• Pim-1 expression was observed in the neointima of balloon-injured rat carotid arteries and in human thoracic aortas and coronary arteries showing intimal thickening suggesting that Pim-1 plays a role in vascular smooth muscle proliferation (PMID:15471855)
• crystal structures of apo Pim-1 kinase and its AMP-PNP (5’-adenylyl-beta,gamma-imidodiphosphate) complex to 2.1-angstroms resolutions (PMID:15525646)
• The structure of the LY294002/Pim-1 complex reveals a new binding mode that may be general for serine-threonine kinases. (PMID:15657054)
• EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth. (PMID:15721354)
• Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway (PMID:15798097)
• Results describe the crystal structures of Pim1 in apo form and bound with AMPPNP. (PMID:15808862)
• PIM1 gene encodes two isoforms by alternative translation initiation at a non-AUG (CUG) and AUG start codons. The two isoforms differ in preferential cellular localization, and may regulate distinct substrates. (PMID:16186805)
• results indicated that chronic Pim-1 kinase overexpression dysregulates cyclin B1 protein expression, which contributes to the development of polyploidy by delaying cytokinesis (PMID:16221667)
• analysis of Pim-1 kinase structure and substrate specificity (PMID:16227208)
• The PIM-1/RPS19 interaction was demonstrated both in vitro and in living cells and led to phosphorylation of RPS19 in an in vitro kinase assay. (PMID:16266891)
• Data suggest that Pim-1 activates Cdc25C by a direct phosphorylation and can thereby assume the function of a positive cell cycle regulator at the G2/M transition. (PMID:16356754)
• All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells (PMID:16403219)
• The large crystals of apo Pim-1 enzyme diffracted to 2.1 A resolution and belong to space group P6(5), with unit-cell parameters a = b = 95.9, c = 80.0 A, beta = 120 degrees. (PMID:16508102)
• The role of LANA from Kaposi sarcoma-associated herpes virus on the upregulation of PIM-1 in B cells is reported. (PMID:16647097)
• results suggest that mammalian RUNX family transcription factors are novel binding partners and substrates for the Pim-1 kinase, which may be able to regulate their activities during normal hematopoiesis as well as in leukemogenesis (PMID:16684349)
• Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells (PMID:16712793)
• Expression of Pim-1 is both necessary and sufficient for polyploidization, but is not critical to cytoplasmic differentiation on megakaryopoiesis. (PMID:17313559)
• Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells (PMID:17327400)
• PIM1 is upregulated after radical prostatectomy for prostatic neoplasms. (PMID:17448597)
• PIM1 mutation is associated with splenic and nodal marginal zone B-cell lymphomas (PMID:17476282)
• the functional role of Pim-1 in molecular processes of head and neck squamous cell carcinomas (PMID:17487358)
• aberration in chromosome 6p21-23, where PIM gene is located, is not a random event in t(12;21) positive ALL (PMID:17560648)
• Results establish a new function for PIM1 as a MYC cofactor that phosphorylates the chromatin at MYC-target loci and suggest that nucleosome phosphorylation, at E boxes, contributes to MYC-dependent transcriptional activation and cellular transformation. (PMID:17643117)
• Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 WAF1 and by promoting cell proliferation. (PMID:17855660)
• Pim-1 is a crucial facet of cardioprotection downstream of Akt (PMID:18037896)
• Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells (PMID:18056989)
• expression of the Myc and Pim proto-oncogenes by Jak2V617F was found to be FERM domain dependent. (PMID:18216297)
• The over-expressions of HSP70 and pim-1 protein/mRNA are related to tumor burden in leukemia patients. (PMID:18426646)
• PIM1 kinase plays a critical role in the STAT3 –> PIM1 –> NFkappaB stress response pathway (PMID:18426800)
• Pim-1 induces the p53 pathway in cultured cells and correlate with increased Mdm2 in mantle cell lymphoma (PMID:18467333)
• Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. (PMID:18519946)
• Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels. (PMID:18593906)
• Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic (PMID:18596907)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pim1	ENSDARG00000100020
mus_musculus	Pim1	ENSMUSG00000024014
rattus_norvegicus	Pim1	ENSRNOG00000000529

Paralogs (2): PIM2 (ENSG00000102096), PIM3 (ENSG00000198355)

Protein

Protein identifiers

Serine/threonine-protein kinase pim-1 — P11309 (reviewed: P11309)

All UniProt accessions (1): P11309

UniProt curated annotations — full annotation on UniProt →

Function. Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Also acts as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis. Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex. Acts as a negative regulator of innate immunity by mediating phosphorylation and inactivation of GBP1 in absence of infection: phosphorylation of GBP1 induces interaction with 14-3-3 protein sigma (SFN) and retention in the cytosol. Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells. Promotes brown adipocyte differentiation.

Subunit / interactions. Interacts with RP9. Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteasomal degradation. Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins. Isoform 2, but not isoform 1, binds BMX. (Microbial infection) Interacts with Epstein-Barr virus EBNA6; this interaction upregulates and stabilizes PIM1 and induces cell proliferation by inhibiting the growth suppressive properties of p21.

Subcellular location. Cytoplasm. Nucleus Cell membrane.

Tissue specificity. Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.

Post-translational modifications. Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation. Ubiquitinated, leading to proteasomal degradation.

Induction. By interferon-gamma (IFNG). Strongly induced in leukocytes by the JAK/STAT pathway in response to cytokines. Induced by different cellular stresses, heat shock and cytotoxic agents.

Miscellaneous. Initiates from CTG codon.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P11309-1	1, Pim-1	yes
P11309-2	2, Pim-1L

RefSeq proteins (2): NP_001230115, NP_002639* (*=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

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 (56 total): helix 15, strand 14, turn 6, modified residue 4, sequence variant 4, mutagenesis site 4, binding site 4, chain 1, domain 1, splice variant 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

191 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3A99	X-RAY DIFFRACTION	1.6
3R04	X-RAY DIFFRACTION	1.7
8R0Q	X-RAY DIFFRACTION	1.7
6NO9	X-RAY DIFFRACTION	1.71
6VRV	X-RAY DIFFRACTION	1.74
6L17	X-RAY DIFFRACTION	1.75
1XWS	X-RAY DIFFRACTION	1.8
2BIK	X-RAY DIFFRACTION	1.8
3VBQ	X-RAY DIFFRACTION	1.85
5N4V	X-RAY DIFFRACTION	1.85
6PDI	X-RAY DIFFRACTION	1.85
4DTK	X-RAY DIFFRACTION	1.86
6YKD	X-RAY DIFFRACTION	1.86
6L12	X-RAY DIFFRACTION	1.87
8R0H	X-RAY DIFFRACTION	1.88
5V82	X-RAY DIFFRACTION	1.89
8R18	X-RAY DIFFRACTION	1.89
2BZH	X-RAY DIFFRACTION	1.9
2BZI	X-RAY DIFFRACTION	1.9
2C3I	X-RAY DIFFRACTION	1.9
2J2I	X-RAY DIFFRACTION	1.9
3F2A	X-RAY DIFFRACTION	1.9
4BZN	X-RAY DIFFRACTION	1.9
4XHK	X-RAY DIFFRACTION	1.9
4ALW	X-RAY DIFFRACTION	1.92
5N50	X-RAY DIFFRACTION	1.92
3R02	X-RAY DIFFRACTION	1.95
5KGG	X-RAY DIFFRACTION	1.95
6L14	X-RAY DIFFRACTION	1.95
7OOW	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11309-F1	90.22	0.86

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): 167 (proton acceptor)

Ligand- & substrate-binding residues (4): 44–52; 67; 121; 128

Post-translational modifications (4): 261, 8, 23, 98

Mutagenesis-validated functional residues (4):

Position	Phenotype
68	increased kinase activity.
81	abolished kinase activity.
82	decreased kinase activity.
193	decreased kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9702518	STAT5 activation downstream of FLT3 ITD mutants
R-HSA-9703465	Signaling by FLT3 fusion proteins
R-HSA-9968551	Regulation of GBP-mediated host defense

MSigDB gene sets: 657 (showing top): VALK_AML_WITH_FLT3_ITD, GSE45365_NK_CELL_VS_CD11B_DC_DN, E2F_Q4, AP1_01, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, DORSAM_HOXA9_TARGETS_UP, E2F4DP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (26): protein phosphorylation (GO:0006468), apoptotic process (GO:0006915), regulation of mitotic cell cycle (GO:0007346), regulation of transmembrane transporter activity (GO:0022898), negative regulation of apoptotic process (GO:0043066), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), positive regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045737), negative regulation of innate immune response (GO:0045824), positive regulation of DNA-templated transcription (GO:0045893), protein autophosphorylation (GO:0046777), protein stabilization (GO:0050821), positive regulation of cardiac muscle cell proliferation (GO:0060045), vitamin D receptor signaling pathway (GO:0070561), cellular response to type II interferon (GO:0071346), positive regulation of protein serine/threonine kinase activity (GO:0071902), positive regulation of brown fat cell differentiation (GO:0090336), regulation of hematopoietic stem cell proliferation (GO:1902033), positive regulation of TORC1 signaling (GO:1904263), positive regulation of cardioblast proliferation (GO:1905062), cellular detoxification (GO:1990748), cellular response to nutrient levels (GO:0031669), cellular response to amino acid starvation (GO:0034198), defense response to bacterium (GO:0042742), cytolysis in another organism (GO:0051715), non-canonical inflammasome complex assembly (GO:0160075), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (13): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), transcription factor binding (GO:0008134), manganese ion binding (GO:0030145), ribosomal small subunit binding (GO:0043024), protein serine/threonine kinase activator activity (GO:0043539), 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), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	1
Signaling by FLT3 ITD and TKD mutants	1
FLT3 signaling in disease	1
GBP-mediated host defense	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein serine/threonine kinase activity	2
protein kinase activity	2
nuclear lumen	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
transmembrane transporter activity	1
regulation of transmembrane transport	1
regulation of molecular function	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein serine/threonine kinase activity	1
positive regulation of cell cycle	1
positive regulation of protein serine/threonine kinase activity	1
positive regulation of cyclin-dependent protein kinase activity	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
protein phosphorylation	1
regulation of protein stability	1
positive regulation of cell population proliferation	1
positive regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
regulation of cardiac muscle cell proliferation	1
hormone-mediated signaling pathway	1
cellular response to vitamin D	1
nuclear receptor-mediated signaling pathway	1

Protein interactions and networks

STRING

1425 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIM1	CDIPT	O14735	914
PIM1	SERPINA1	P01009	862
PIM1	SERPINA3	P01011	593
PIM1	PPP1R7	Q15435	550
PIM1	MMUT	P22033	526
PIM1	UCK2	Q9BZX2	517
PIM1	EIF4EBP1	Q13541	501
PIM1	TMBIM4	Q9HC24	498
PIM1	HPN	P05981	492
PIM1	SOCS1	O15524	492
PIM1	RHOH	Q15669	456
PIM1	ATP2A2	P16614	434
PIM1	SERPINI1	Q99574	423
PIM1	BCL6	P41182	402
PIM1	KDR	P35968	397

IntAct

47 interactions, top by confidence:

A	B	Type	Score
RPS19	PIM1	psi-mi:“MI:0915”(physical association)	0.630
PIM1	RPS19	psi-mi:“MI:0915”(physical association)	0.630
RPS19	PIM1	psi-mi:“MI:0217”(phosphorylation reaction)	0.630
TFPT	PIM1	psi-mi:“MI:0915”(physical association)	0.560
PIM1	FH	psi-mi:“MI:0915”(physical association)	0.560
FXR2	PIM1	psi-mi:“MI:0915”(physical association)	0.560
NHLH1	PIM1	psi-mi:“MI:0915”(physical association)	0.560
BEND7	PIM1	psi-mi:“MI:0915”(physical association)	0.560
BANP	PIM1	psi-mi:“MI:0915”(physical association)	0.560
PIM1	HEXIM2	psi-mi:“MI:0915”(physical association)	0.560
PIM1	ZBTB1	psi-mi:“MI:0915”(physical association)	0.560
PIM1	TFPT	psi-mi:“MI:0915”(physical association)	0.560
FH	PIM1	psi-mi:“MI:0915”(physical association)	0.560
PIM1	FXR2	psi-mi:“MI:0915”(physical association)	0.560
PIM1	BEND7	psi-mi:“MI:0915”(physical association)	0.560
HEXIM2	PIM1	psi-mi:“MI:0915”(physical association)	0.560
ZBTB1	PIM1	psi-mi:“MI:0915”(physical association)	0.560
PIM1	NHLH1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (130): PIM1 (Two-hybrid), PIM1 (Two-hybrid), FXR2 (Two-hybrid), ZBTB1 (Two-hybrid), TFPT (Two-hybrid), BANP (Two-hybrid), HEXIM2 (Two-hybrid), BEND7 (Two-hybrid), PIM1 (Two-hybrid), EDC3 (Affinity Capture-MS), DCP1B (Affinity Capture-MS), DCP1A (Affinity Capture-MS), DDX6 (Affinity Capture-MS), MARK3 (Affinity Capture-MS), DCAF4 (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

69 interactions.

A	Effect	B	Mechanism
PIM1	down-regulates	MARK3	phosphorylation
PIM1	up-regulates	RPS19	phosphorylation
PIM1	“down-regulates activity”	H3C1	phosphorylation
PIM1	“up-regulates quantity by stabilization”	CDKN1A	phosphorylation
PIM1	“up-regulates quantity by stabilization”	MDM2	phosphorylation
PIM1	up-regulates	MDM2	phosphorylation
PIM1	down-regulates	CDKN1B	phosphorylation
PIM1	“down-regulates activity”	CDKN1B	phosphorylation
PIM1	down-regulates	FOXO3	phosphorylation
PIM1	“down-regulates activity”	FOXO3	phosphorylation
PIM1	down-regulates	MAP3K5	phosphorylation
PIM1	up-regulates	RELA	phosphorylation
SGI-1776	down-regulates	PIM1	“chemical inhibition”
STAT5A	“up-regulates quantity by expression”	PIM1	“transcriptional regulation”
PIM1	“down-regulates activity”	BAD	phosphorylation
PIM1	down-regulates	FOXO	phosphorylation
ERG	“up-regulates quantity by expression”	PIM1	“transcriptional regulation”
PRKACA	“up-regulates activity”	PIM1	phosphorylation
PIM1	“up-regulates activity”	SKP2	phosphorylation
PIM1	“down-regulates activity”	FZR1	phosphorylation
PIM1	“up-regulates quantity”	FLT3	phosphorylation
PIM1	“up-regulates activity”	MYC	phosphorylation
HOXA9	“up-regulates quantity by expression”	PIM1	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — DLBCLNOS, NHL, PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997072	GRCh37/hg19 6p21.31-21.2(chr6:34401304-38435497)	Pathogenic

SpliceAI

515 predictions. Top by Δscore:

Variant	Effect	Δscore
6:37170653:GCCCG:G	donor_gain	1.0000
6:37170654:CCCGG:C	donor_loss	1.0000
6:37170656:CGG:C	donor_loss	1.0000
6:37170657:GGT:G	donor_loss	1.0000
6:37170658:G:GG	donor_gain	1.0000
6:37170658:GTGAG:G	donor_loss	1.0000
6:37170659:T:A	donor_loss	1.0000
6:37170768:CCTA:C	acceptor_loss	1.0000
6:37170771:A:AG	acceptor_gain	1.0000
6:37170771:A:AT	acceptor_loss	1.0000
6:37170771:AG:A	acceptor_gain	1.0000
6:37170772:G:GT	acceptor_gain	1.0000
6:37170772:GG:G	acceptor_gain	1.0000
6:37170772:GGC:G	acceptor_gain	1.0000
6:37170772:GGCA:G	acceptor_gain	1.0000
6:37170772:GGCAA:G	acceptor_gain	1.0000
6:37170875:TGCCG:T	donor_gain	1.0000
6:37170876:GCCG:G	donor_gain	1.0000
6:37170876:GCCGG:G	donor_gain	1.0000
6:37170878:CGG:C	donor_loss	1.0000
6:37170880:G:GG	donor_gain	1.0000
6:37170880:GT:G	donor_loss	1.0000
6:37170881:T:G	donor_loss	1.0000
6:37170975:TTCCA:T	acceptor_loss	1.0000
6:37170976:TCCA:T	acceptor_loss	1.0000
6:37170977:CCAG:C	acceptor_loss	1.0000
6:37170978:CA:C	acceptor_loss	1.0000
6:37170979:AGG:A	acceptor_loss	1.0000
6:37171028:GCTG:G	donor_gain	1.0000
6:37171030:TGGT:T	donor_loss	1.0000

AlphaMissense

2049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:37170823:G:C	G45R	1.000
6:37170830:G:A	G47D	1.000
6:37170835:T:A	F49I	1.000
6:37170835:T:C	F49L	1.000
6:37170837:C:A	F49L	1.000
6:37170837:C:G	F49L	1.000
6:37170838:G:C	G50R	1.000
6:37170839:G:A	G50D	1.000
6:37170839:G:T	G50V	1.000
6:37170854:G:A	G55D	1.000
6:37170985:C:A	A65D	1.000
6:37170990:A:G	K67E	1.000
6:37170992:A:C	K67N	1.000
6:37170992:A:T	K67N	1.000
6:37171144:C:A	P87H	1.000
6:37171149:G:A	E89K	1.000
6:37171270:T:C	L129P	1.000
6:37171272:T:A	F130I	1.000
6:37171272:T:C	F130L	1.000
6:37171274:C:A	F130L	1.000
6:37171274:C:G	F130L	1.000
6:37171358:C:G	C158W	1.000
6:37171381:G:C	R166P	1.000
6:37171383:G:C	D167H	1.000
6:37171384:A:C	D167A	1.000
6:37171384:A:G	D167G	1.000
6:37171384:A:T	D167V	1.000
6:37171385:C:A	D167E	1.000
6:37171385:C:G	D167E	1.000
6:37171389:A:C	K169Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000101963 (6:37172079 CAG>C), RS1001162519 (6:37170223 G>C,T), RS1002062005 (6:37170969 C>G,T), RS1002449184 (6:37175581 C>G,T), RS1002712581 (6:37174444 C>A,T), RS1002786706 (6:37174229 A>C,G), RS1002788613 (6:37169568 C>T), RS1003700290 (6:37175294 C>A,T), RS1004138330 (6:37168831 C>A), RS1004145562 (6:37169984 C>G,T), RS1004472450 (6:37170119 C>T), RS1004543891 (6:37174495 A>C), RS1005010842 (6:37170487 C>A,T), RS1005287062 (6:37169544 C>G), RS1005688815 (6:37175516 G>A,C,T)

Disease associations

OMIM: gene MIM:164960 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2147 (SINGLE PROTEIN), CHEMBL3430900 (PROTEIN-PROTEIN INTERACTION), CHEMBL3559682 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 547,481 (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
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4	69,932
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL479	THIORIDAZINE	4	21,859
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL960	LEFLUNOMIDE	4	52,218
CHEMBL165	RESVERATROL	3	60,144
CHEMBL1908391	MASITINIB	3	2,808
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL50	QUERCETIN	3	74,559
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1980715	LAUROGUADINE	2	294
CHEMBL2386889	SCH-900776	2	740
CHEMBL362558	LY-2090314	2	108
CHEMBL3975308	NUVISERTIB	2	100
CHEMBL4277900	CROZBACICLIB	2
CHEMBL4467168	DAPOLSERTIB	2
CHEMBL4868568	MONZOSERTIB	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL1908394	GSK-461364	1
CHEMBL1952329	SGI-1776	1
CHEMBL3544966	GSK-1059615	1
CHEMBL3651966	LGH-447	1
CHEMBL494089	GSK-690693	1

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
PIM1 L2V	Ibrutinib	Diffuse Large B-cell Lymphoma Activated B-cell Type	Resistance	CIViC D	EID9945
PIM1 P81S	Ibrutinib	Diffuse Large B-cell Lymphoma Activated B-cell Type	Resistance	CIViC D	EID9946
PIM1 S97N	Ibrutinib	Diffuse Large B-cell Lymphoma Activated B-cell Type	Resistance	CIViC D	EID9947

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 (20 total), top 20:

Ligand	Action	Affinity	Parameter
LGB321	Inhibition	12.0	pKi
PIM447	Inhibition	11.22	pKi
AZD1208	Inhibition	10.77	pKi
GDC-0339	Inhibition	10.52	pKi
uzansertib	Inhibition	9.62	pIC50
leucettine L41	Inhibition	8.39	pIC50
nuvisertib	Inhibition	8.3	pKi
compound 14k [PMID: 21982499]	Inhibition	8.3	pIC50
CX-6258	Inhibition	8.3	pIC50
SGI-1776	Inhibition	8.15	pIC50
XL413	Inhibition	7.38	pIC50
compound 28 [PMID: 30624936]	Inhibition	7.3	pIC50
compound 20 [PMID: 22136433]	Inhibition	7.22	pIC50
voruciclib	Inhibition	7.14	pIC50
ruboxistaurin	Inhibition	6.7	pIC50
silmitasertib	Inhibition	6.67	pIC50
compound 2 [PMID: 22560567]	Inhibition	6.48	pIC50
Akt inhibitor X	Inhibition	5.89	pIC50
CX-5011	Inhibition	5.6	pIC50
CX-5279	Inhibition	5.07	pIC50

Binding affinities (BindingDB)

2972 measured of 3744 human assays (3748 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-6-[2,6-difluoro-4-(1-hydroxycyclopropyl)phenyl]-5-fluoropyridine-2-carboxamide	KI	0.001 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluoro-3-methoxyphenyl)-1,3-thiazole-4-carboxamide	KI	0.001 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(3-ethoxy-2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.001 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3-methoxy-3-methylazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluoro-3-iodophenyl)-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5S)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluoro-3-iodophenyl)-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(1R,4S,5R)-4-amino-8-oxabicyclo[3.2.1]octan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(4-chloro-2-fluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-indazol-2-yl-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[2,6-difluoro-4-[(1S)-1-fluoroethyl]phenyl]-1,3-thiazole-4-carboxamide	KI	0.002 nM	US-9963446: Oxepan-2-yl-pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[2,6-difluoro-4-[(3S)-oxolan-3-yl]oxyphenyl]-1,3-thiazole-4-carboxamide	KI	0.00224 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[1-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-3-imino-1-methyliminopropan-2-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3,3-difluoro-5-methylazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2R,5S,7R)-5-amino-7-methyloxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[2,6-difluoro-4-[(3R)-oxolan-3-yl]oxyphenyl]-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluoro-4-methylphenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,3,6-trifluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[2-fluoro-4-(3-methyloxetan-3-yl)phenyl]-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2R,4R,5S,6R)-4-amino-5-hydroxy-5,6-dimethyloxan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.003 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.00342 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3,3-difluoroazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5S)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,5-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(8-amino-9-methoxy-5-azaspiro[2.6]nonan-5-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-(5-ethyl-3-pyridinyl)-3-(6-piperazin-1-yl-2-pyridinyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-pyrazolo[3,4-c]pyridine	KI	0.004 nM	US-9260425: Pyrazolo[3,4-c]pyridine compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,3-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,3,6-trifluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(3-methyl-2-pyridinyl)-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[(4R)-6,8-difluoro-4-hydroxy-3,4-dihydro-2H-chromen-7-yl]-1,3-thiazole-4-carboxamide	KI	0.004 nM	US-9963446: Oxepan-2-yl-pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6R,7S)-5-amino-6-fluoro-7-methyloxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.005 nM	US-9963446: Oxepan-2-yl-pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2-fluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.00509 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[1-[(5S)-5-amino-3,3-difluoroazepan-1-yl]-3-imino-1-methyliminopropan-2-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(3,3-difluoro-5-hydroxyazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3,3-difluoroazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluoro-4-methoxyphenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-6-[2,6-difluoro-4-(4-hydroxyoxan-4-yl)phenyl]-5-fluoropyridine-2-carboxamide	KI	0.006 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S,7R)-5-amino-6-methoxy-7-methyloxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-9963446: Oxepan-2-yl-pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(1S,4S,5S)-4-amino-8-oxabicyclo[3.2.1]octan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.006 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
3-amino-N-[5-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-6-(2-fluorophenyl)pyrazine-2-carboxamide	KI	0.007 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3-methoxyazepan-1-yl)-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-1-cyclopropylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[3,3-difluoro-5-(methylamino)azepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,6-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2-fluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(1,5-dimethylpyrazol-4-yl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(2-fluoro-6-methylphenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl]-1-methylpyrazol-4-yl]-2-(5-chloro-2-fluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-(3-chloro-2-fluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-6-(4-chloro-2-fluorophenyl)-5-fluoropyridine-2-carboxamide	KI	0.007 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
N-[5-[(2S,5R,6S)-5-amino-6-fluorooxepan-2-yl]-1-methylpyrazol-4-yl]-2-[2,6-difluoro-4-(3-hydroxyoxolan-3-yl)phenyl]-1,3-thiazole-4-carboxamide	KI	0.00762 nM	US-9328106: Cyclic ether pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-[(5R)-5-amino-3,3-difluoroazepan-1-yl]-1-methylpyrazol-4-yl]-2-(2,5-difluorophenyl)-1,3-thiazole-4-carboxamide	KI	0.008 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use
5-amino-N-[5-(5-amino-3,3-difluoroazepan-1-yl)-1-methylpyrazol-4-yl]-2-(3,5-difluoro-4-pyridinyl)-1,3-thiazole-4-carboxamide	KI	0.008 nM	US-8614206: Pyrazol-4-yl-heterocyclyl-carboxamide compounds and methods of use

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL3318854
11.00	Ki	0.01	nM	CHEMBL3634783
11.00	IC50	0.01	nM	CHEMBL3691937
11.00	IC50	0.01	nM	CHEMBL3691967
11.00	IC50	0.01	nM	CHEMBL3687493
11.00	IC50	0.01	nM	CHEMBL3687509
11.00	IC50	0.01	nM	CHEMBL3687474
11.00	Ki	0.01	nM	CHEMBL3648671
11.00	Ki	0.01	nM	CHEMBL3648682
11.00	Ki	0.01	nM	CHEMBL3648693
11.00	Ki	0.01	nM	CHEMBL3648717
11.00	Ki	0.01	nM	CHEMBL3648722
11.00	Ki	0.01	nM	CHEMBL3648752
11.00	Ki	0.01	nM	CHEMBL3648822
11.00	Ki	0.01	nM	CHEMBL3894581
11.00	Ki	0.01	nM	CHEMBL3972110
11.00	Ki	0.01	nM	CHEMBL3919573
11.00	Ki	0.01	nM	CHEMBL4108653
11.00	Ki	0.01	nM	CHEMBL4113050
11.00	Ki	0.01	nM	CHEMBL4439756
11.00	Ki	0.01	nM	CHEMBL3676285
11.00	Ki	0.01	nM	CHEMBL6035052
10.96	Ki	0.011	nM	CHEMBL2387479
10.96	Ki	0.011	nM	CHEMBL4111174
10.96	Ki	0.011	nM	CHEMBL4109372
10.96	Ki	0.011	nM	CHEMBL4112826
10.96	Ki	0.011	nM	CHEMBL5895690
10.92	Ki	0.012	nM	CHEMBL3648826
10.92	Ki	0.012	nM	CHEMBL4110434
10.92	IC50	0.012	nM	CHEMBL3902148
10.92	Ki	0.012	nM	CHEMBL3959091
10.89	Ki	0.013	nM	CHEMBL3634760
10.89	Ki	0.013	nM	CHEMBL3639476
10.89	Ki	0.013	nM	CHEMBL3949620
10.89	Ki	0.013	nM	CHEMBL4115609
10.89	Ki	0.013	nM	CHEMBL3943948
10.89	Ki	0.013	nM	CHEMBL4113395
10.89	IC50	0.013	nM	CHEMBL3895124
10.88	Ki	0.0131	nM	CHEMBL3939366
10.86	Ki	0.0137	nM	CHEMBL4111122
10.85	Ki	0.014	nM	CHEMBL3648793
10.85	Ki	0.014	nM	CHEMBL3648823
10.85	Ki	0.014	nM	CHEMBL3922596
10.85	Ki	0.014	nM	CHEMBL4115489
10.85	Ki	0.014	nM	CHEMBL3925594
10.85	Ki	0.014	nM	CHEMBL3925922
10.85	Ki	0.014	nM	CHEMBL3911768
10.85	Ki	0.014	nM	CHEMBL4107753
10.85	Ki	0.014	nM	CHEMBL4109272
10.85	Ki	0.014	nM	CHEMBL4109861

PubChem BioAssay actives

2238 with measured affinity, of 6100 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	1692889: Inhibition of PIM1 (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	1256221: Inhibition of Pim1 (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	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
(3S,5R)-3,5-diamino-1-[3-[[2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-yl]amino]-4-pyridinyl]piperidin-4-ol	1325330: Inhibition of recombinant Pim1 (unknown origin) by electrochemiluminescence assay	ic50	<0.0001	uM
1-[6-(1,4-diazepan-1-yl)-2-pyridinyl]-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridazine	1483004: Inhibition of PIM1 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM
2-[(1-methylcyclopropyl)amino]-3-[(1S)-1-(1-methylimidazol-4-yl)ethyl]-8-[(6R)-6-methyl-4-oxo-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-2-yl]quinazolin-4-one	1572116: Inhibition of full length recombinant PIM1 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay	ic50	<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	1520508: Inhibition of recombinant human PIM1 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	1520508: Inhibition of recombinant human PIM1 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	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
2-[(1-methylcyclopropyl)amino]-3-[1-(1-methylimidazol-4-yl)ethyl]-8-[(6R)-6-methyl-4-oxo-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-2-yl]quinazolin-4-one	1572116: Inhibition of full length recombinant PIM1 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay	ic50	<0.0001	uM
3-[(1-aminocyclopropyl)methyl]-2-[(1-methylcyclopropyl)amino]-8-[(6R)-6-methyl-4-oxo-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-2-yl]quinazolin-4-one	1572116: Inhibition of full length recombinant PIM1 (unknown origin) assessed as reduction in BAD phosphorylation at Ser112 residues preincubated for 30 mins followed by biotinylated BAD addition and measured after 1 hr by HTRF assay	ic50	<0.0001	uM
3-amino-N-[4-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]-6-(2,6-difluorophenyl)pyridine-2-carboxamide	1062194: Inhibition of PIM1 (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	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
N-[4-[(1R,3S,5S)-3-amino-5-methylcyclohexyl]-3-pyridinyl]-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide	1266531: Inhibition of PIM1 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	1062196: Inhibition of PIM1 (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	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-(2-phenylethylamino)-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
(5Z)-5-[[2-[(3R)-3-aminopiperidin-1-yl]-3-phenylphenyl]methylidene]-1,3-thiazolidine-2,4-dione	1062196: Inhibition of PIM1 (unknown origin)	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	1062196: Inhibition of PIM1 (unknown origin)	ki	<0.0001	uM
3-amino-N-[4-[(3S)-3-aminopiperidin-1-yl]-3-pyridinyl]-6-(2-fluorophenyl)pyridine-2-carboxamide	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	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	1062196: Inhibition of PIM1 (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	1325330: Inhibition of recombinant Pim1 (unknown origin) by electrochemiluminescence assay	ic50	<0.0001	uM
N-[4-[(3S,4R)-3-amino-4-methylpiperidin-1-yl]-3-pyridinyl]-2-(2,6-difluorophenyl)imidazo[1,5-b]pyridazin-7-amine	1325330: Inhibition of recombinant Pim1 (unknown origin) by electrochemiluminescence assay	ic50	<0.0001	uM
(3S)-1-[6-(5-pyridin-3-yl-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-pyridinyl]piperidin-3-amine	1483004: Inhibition of PIM1 (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	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins	ki	<0.0001	uM
3-ethyl-5-[3-(6-piperazin-1-yl-2-pyridinyl)-1H-pyrazolo[3,4-c]pyridin-5-yl]pyrimidin-4-one	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (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	1483004: Inhibition of PIM1 (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	1256221: Inhibition of Pim1 (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	1256221: Inhibition of Pim1 (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	749898: Inhibition of PIM1 (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	1520508: Inhibition of recombinant human PIM1 using FAM-pimtide as substrate after 90 mins by Z-LYTE assay	ki	<0.0001	uM
5-(piperidin-4-ylmethylamino)-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (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-(piperidin-4-ylmethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (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[3,2-b]pyridin-3-yl]-5-(piperidin-4-ylmethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (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	749898: Inhibition of PIM1 (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-(piperidin-4-ylmethoxy)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (unknown origin) using FAM-pimtide as substrate after 90 mins by spectrophotometry in presence of ATP	ki	<0.0001	uM
5-[[(3R,4R)-3-fluoropiperidin-4-yl]methylamino]-N-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide	749898: Inhibition of PIM1 (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	749898: Inhibition of PIM1 (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	749898: Inhibition of PIM1 (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	749898: Inhibition of PIM1 (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	1483004: Inhibition of PIM1 (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	749898: Inhibition of PIM1 (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	1520508: Inhibition of recombinant human PIM1 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	1520508: Inhibition of recombinant human PIM1 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	1483004: Inhibition of PIM1 (unknown origin) using 5FAM-ARKRRRHPSGPPTA as substrate after 90 mins in presence of ATP by caliper microfluidic mobility shift assay	ki	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	4
(+)-JQ1 compound	affects cotreatment, affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	4
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	4
Tretinoin	increases expression	4
Valproic Acid	affects expression, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
nickel sulfate	increases expression	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Copper	affects binding, increases expression, decreases expression	2
Hydrogen Peroxide	decreases expression, decreases reaction, affects expression	2
Progesterone	affects cotreatment, decreases expression, affects expression, increases reaction	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
Genistein	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
OTX015	decreases expression	1
bisphenol F	increases expression	1
PF-06840003	decreases expression, decreases reaction	1
TL8-506	affects cotreatment, increases expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1

ChEMBL screening assays

1008 unique, capped per target: 971 binding, 30 functional, 4 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001350	Binding	Inhibition of PIM1 at 10 uM	Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines. — Bioorg Med Chem Lett
CHEMBL1963726	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PIM1	PubChem BioAssay data set
CHEMBL3100556	ADMET	Drug degradation in NEB buffer assessed as PIM1 kinase (unknown origin)-mediated H3-pSer-CoA formation at 1 mg after 60 mins by RP-HPLC analysis	Azide-alkyne cycloaddition affording enzymatically tunable bisubstrate based inhibitors of histone acetyltransferase PCAF. — Bioorg Med Chem Lett

Cellosaurus cell lines

12 cell lines: 10 cancer cell line, 1 transformed cell line, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2022	DND-41	Cancer cell line	Male
CVCL_D3X9	ARSI	Cancer cell line	Female
CVCL_D5KS	TMD12	Cancer cell line	Male
CVCL_D7XF	Ubigene A-549 PIM1 KO	Cancer cell line	Male
CVCL_D8SX	Ubigene HCT 116 PIM1 KO	Cancer cell line	Male
CVCL_D9ND	Ubigene HEK293 PIM1 KO	Transformed cell line	Female
CVCL_E0KR	Ubigene HeLa PIM1 KO	Cancer cell line	Female
CVCL_E0ZM	Ubigene NCI-H1299 PIM1 KO	Cancer cell line	Male
CVCL_TD76	HAP1 PIM1 (-) 1	Cancer cell line	Male
CVCL_TD77	HAP1 PIM1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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