ACVR1B

Summary

ACVR1B (activin A receptor type 1B, HGNC:172) is a protein-coding gene on chromosome 12q13.13, encoding Activin receptor type-1B (P36896). Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B).

This gene encodes an activin A type IB receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 91 — RefSeq curated summary.

At a glance

• Gene–disease (curated): malignant pancreatic neoplasm (No Known Disease Relationship, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 54 total — 4 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• MANE Select transcript: NM_004302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:172
Approved symbol	ACVR1B
Name	activin A receptor type 1B
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	ALK4, SKR2, ActRIB
Ensembl gene	ENSG00000135503
Ensembl biotype	protein_coding
OMIM	601300
Entrez	91

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000257963, ENST00000415850, ENST00000426655, ENST00000536420, ENST00000541224, ENST00000542485, ENST00000563121, ENST00000900345, ENST00000900346, ENST00000900347, ENST00000900348, ENST00000900349, ENST00000900350, ENST00000916256

RefSeq mRNA: 15 — MANE Select: NM_004302 NM_001412774, NM_001412775, NM_001412776, NM_001412777, NM_001412778, NM_001412779, NM_001412780, NM_001412781, NM_001412782, NM_001412784, NM_001412785, NM_001412786, NM_004302, NM_020327, NM_020328

CCDS: CCDS44893, CCDS44894, CCDS8816

Canonical transcript exons

ENST00000257963 — 9 exons

Exon	Start	End
ENSE00000837888	51976327	51976575
ENSE00000837889	51980969	51981199
ENSE00000837890	51983999	51984166
ENSE00000837892	51986818	51986942
ENSE00000919840	51991863	51991993
ENSE00000939414	51993985	51997078
ENSE00002295292	51951699	51951834
ENSE00003505810	51985192	51985348
ENSE00003668967	51975265	51975504

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8576 / max 149.5984, expressed in 1754 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125534	9.8576	1754

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.76	gold quality
oocyte	CL:0000023	99.40	gold quality
middle temporal gyrus	UBERON:0002771	97.96	gold quality
pancreatic ductal cell	CL:0002079	97.70	gold quality
renal medulla	UBERON:0000362	97.53	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.30	gold quality
type B pancreatic cell	CL:0000169	96.63	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.55	gold quality
parotid gland	UBERON:0001831	96.17	gold quality
cervix squamous epithelium	UBERON:0006922	95.88	gold quality
nephron tubule	UBERON:0001231	95.61	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.27	gold quality
frontal pole	UBERON:0002795	95.25	gold quality
jejunal mucosa	UBERON:0000399	95.18	gold quality
esophagus squamous epithelium	UBERON:0006920	95.14	gold quality
squamous epithelium	UBERON:0006914	95.06	gold quality
cortical plate	UBERON:0005343	94.85	gold quality
kidney epithelium	UBERON:0004819	94.82	gold quality
epithelium of esophagus	UBERON:0001976	94.62	gold quality
gingival epithelium	UBERON:0001949	94.53	gold quality
bronchial epithelial cell	CL:0002328	94.48	gold quality
epithelium of bronchus	UBERON:0002031	94.40	gold quality
bronchus	UBERON:0002185	94.30	gold quality
adult organism	UBERON:0007023	94.21	gold quality
upper leg skin	UBERON:0004262	94.09	gold quality
orbitofrontal cortex	UBERON:0004167	94.05	gold quality
metanephric glomerulus	UBERON:0004736	93.97	gold quality
renal glomerulus	UBERON:0000074	93.93	gold quality
colonic mucosa	UBERON:0000317	93.86	gold quality
gingiva	UBERON:0001828	93.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD7

miRNA regulators (miRDB)

81 targeting ACVR1B, 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-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4269	99.55	69.89	1373

Literature-anchored findings (GeneRIF, showing 39)

• distribution in gestational tissues across human pregnancy and during labour (PMID:11969340)
• data indicate that truncated Alk4 isoforms interfere with activin signaling pathways and thereby may contribute to uncontrolled cell growth (PMID:12364468)
• Activin signaling mediated by ActRIB-Smad2 system in the ovary may thus be essential for the regulation of follicular differentiation. (PMID:12639945)
• there is only a partial overlap of the binding sites on ALK4 and ALK3 for activin-A and bone morphogenetic protein-2, respectively (PMID:12665502)
• ALK4 binds to activin at a specific site in order to signal via type II receptors (PMID:15123686)
• Dpr2 binds to the TGFbeta receptors ALK5 and ALK4, and accelerates lysosomal degradation of these receptors (PMID:15459392)
• findings indicate a new inhibitory function of FKBP12 as an adaptor molecule for the Smad7-Smurf1 complex to regulate the duration of the activin signal through activin type I receptors (PMID:16720724)
• a regulation mode of miR-24 on erythropoiesis by impeding ALK4 expression. (PMID:17906079)
• Study indicate that the synthetic h-CFC interacts with the ALK4 receptor with a K(D) in micro M range, that the h-CFC overall topology is determined by the presence of three disulfide bridges. (PMID:19035567)
• activin A signal is transduced through the activin A type 1 receptor, ALK4, and transactivates several TGF-beta target genes in a SMAD-independent manner. (PMID:20226172)
• We applied a two-stage fine mapping approach, and are the first to identify and partially replicate genetic variants in the ACVR1B gene that account for genetic variation in human muscle strength. (PMID:21063444)
• Activin A-ACVRIB/ALK4-Smad-dependent collagen production was augmented in SSc fibroblasts, suggesting the involvement of this signaling mechanism in systemic sclerosis. (PMID:21377836)
• Inhibin alpha-subunit N terminus interacts with activin type IB receptor to disrupt activin signaling. (PMID:22267736)
• Act A protein levels were significantly higher in NTM tissues compared to GTM tissues. (PMID:23010638)
• ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers. (PMID:23159635)
• Findings define a regulatory role of miR-98 in tumor angiogenesis and invasion through repressed ALK4 and MMP11 expression. (PMID:23211491)
• The deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in pancreatic cancer. (PMID:24886203)
• ACVR1B functions as a positive regulator of monocyte/macrophage differentiation. ACVR1B knockdown promoted THP-1 proliferation by increasing Rb phosphorylation. Down-regulation reduced p-Smad2/3 and C/EBPalpha, inhibiting monocyte/macrophage differentiation. (PMID:25258381)
• This study demonstrated positive regulation of monocyte/macrophage differentiation by lnc-MC and uncovered an elaborate regulation mechanism composed of PU.1, lnc-MC, miR-199a-5p, and ACVR1B. (PMID:26149389)
• ALK4 is expressed in male germ cells and Sertoli cells. (PMID:26289399)
• Data suggest that activin A up-regulates SNAIL expression via ALK4/ACVR1B-induced SMAD signaling in trophoblast cells; elevated SNAIL contributes to up-regulation of MMP2 expression which plays key role in promoting trophoblast cell invasion. (PMID:26305619)
• in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. (PMID:27253421)
• Results showed that ACVR1B expression is upregulated during latent infection with a miR-UL148D deletion virus. Data indicates miR-UL148D inhibits ACVR1B expression in latently infected cells to limit proinflammatory cytokine secretion. (PMID:27491954)
• It was concluded that ALK4 inhibition increases myogenesis but also regulates the tight balance of protein synthesis and degradation. (PMID:27733450)
• ALK4 is an important profibrotic signaling molecule in the post-MI CF. Haplodeficiency of ALK4 significantly improved LV function and survival rate by attenuating CF in vivo, ameliorated (PMID:28214509)
• Our study provided experimental and clinical evidence for the involvement of activin A and ALK4 in the pathophysiology of atrial fibrosis and atrial fibrillation (PMID:28639003)
• Overexpression of ALK4 suppressed glioma cell proliferation, migration and invasion through the inactivation of JAK/STAT3 signaling pathway. (PMID:29278854)
• Multiple emphysema apicobasal distribution loci colocalize to regulatory elements that are active across multiple tissues and cell types, and functional analyses confirm the presence of an emphysema apicobasal distribution-associated functional variant that regulates ACVR1B expression, indicating that transforming growth factor-b signaling plays a role in the emphysema apicobasal distribution phenotype. (PMID:30335480)
• Expression of ALK4 is upregulated in atrial fibrillation human atrium, with higher ALK4 expression in AF human atrium underlying hypertension. (PMID:30369314)
• Blockade of ALK4/5 signaling suppresses cadmium- and erastin-induced cell death in renal proximal tubular epithelial cells via distinct signaling mechanisms. (PMID:30804470)
• Toxoplasma activates HIF-1 by stabilizing the HIF-1alpha subunit, and this is dependent on the signaling from the the Activin-Like Kinase (ALK) receptor superfamily protein, ALK4. (PMID:30891432)
• ALK4-SMAD3/4 mediates the effects of activin A on the upregulation of PAI-1 in human granulosa lutein cells. (PMID:31982478)
• Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies. (PMID:31990347)
• Activin A increases human trophoblast invasion by upregulating integrin beta1 through ALK4. (PMID:33230889)
• [Involvement of Notch1 and ALK4/5 Signaling Pathways in Renal Tubular Cell Death: Their Application to Clarification of Cadmium Toxicity]. (PMID:33342936)
• Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population. (PMID:34666056)
• Lack of Tgfbr1 and Acvr1b synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration. (PMID:35323108)
• Activin receptor ALK4 promotes adipose tissue hyperplasia by suppressing differentiation of adipocyte precursors. (PMID:36403856)
• Abundance of ACVR1B transcript is elevated during septic conditions: Perspectives obtained from a hands-on reductionist investigation. (PMID:37020544)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	acvr1ba	ENSDARG00000018968
danio_rerio	acvr1bb	ENSDARG00000052142
mus_musculus	Acvr1b	ENSMUSG00000000532
rattus_norvegicus	Acvr1b	ENSRNOG00000006934
drosophila_melanogaster	tkv	FBGN0003716
drosophila_melanogaster	babo	FBGN0011300
caenorhabditis_elegans		WBGENE00000897
caenorhabditis_elegans		WBGENE00004860

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Activin receptor type-1B — P36896 (reviewed: P36896)

Alternative names: Activin receptor type IB, Activin receptor-like kinase 4, Serine/threonine-protein kinase receptor R2

All UniProt accessions (2): P36896, F5H5Q2

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.

Subunit / interactions. Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3. Interacts with SMAD2 and SMAD3. Interacts with SMAD7. Interacts with FKBP1A. Interacts with IGSF1. Interacts with CRIPTO. Interacts with TDP2. Interacts with TSC22D1/TSC-22.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in many tissues, most strongly in kidney, pancreas, brain, lung, and liver.

Post-translational modifications. Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7. Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex. Ubiquitinated.

Disease relevance. ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis.

Activity regulation. Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.

Domain organisation. The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P36896-1	1, SKR2-1	yes
P36896-2	2, SKR2-2
P36896-3	3, SKR2-3
P36896-4	4
P36896-5	5

RefSeq proteins (15): NP_001399703, NP_001399704, NP_001399705, NP_001399706, NP_001399707, NP_001399708, NP_001399709, NP_001399710, NP_001399711, NP_001399713, NP_001399714, NP_001399715, NP_004293, NP_064732, NP_064733 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR003605	GS_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00069, PF01064, PF08515

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (37 total): mutagenesis site 6, strand 6, splice variant 4, sequence variant 3, topological domain 2, sequence conflict 2, helix 2, turn 2, domain 2, binding site 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7MRZ	X-RAY DIFFRACTION	3
7OLY	X-RAY DIFFRACTION	3.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36896-F1	84.09	0.61

Antibody-complex structures (SAbDab): 2 — 7MRZ, 7OLY

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): 335 (proton acceptor)

Ligand- & substrate-binding residues (2): 213–221; 234

Post-translational modifications (1): 380

Glycosylation sites (1): 43

Mutagenesis-validated functional residues (6):

Position	Phenotype
40	increases binding to activin.
70	decreases binding to activin.
73	increases binding to activin.
75	decreases binding to activin.
77	decreases binding to activin.
206	leads to constitutive activation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-1502540	Signaling by Activin
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 366 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GGGACCA_MIR133A_MIR133B, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ERYTHROCYTE_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, AAGCCAT_MIR135A_MIR135B, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (26): G1/S transition of mitotic cell cycle (GO:0000082), in utero embryonic development (GO:0001701), hair follicle development (GO:0001942), regulation of DNA-templated transcription (GO:0006355), signal transduction (GO:0007165), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), nervous system development (GO:0007399), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), peptidyl-threonine phosphorylation (GO:0018107), negative regulation of ossification (GO:0030279), negative regulation of cell growth (GO:0030308), activin receptor signaling pathway (GO:0032924), positive regulation of activin receptor signaling pathway (GO:0032927), nodal signaling pathway (GO:0038092), negative regulation of cell differentiation (GO:0045596), positive regulation of erythrocyte differentiation (GO:0045648), protein autophosphorylation (GO:0046777), cellular response to growth factor stimulus (GO:0071363), extrinsic apoptotic signaling pathway (GO:0097191), positive regulation of trophoblast cell migration (GO:1901165), protein phosphorylation (GO:0006468), regulation of signal transduction (GO:0009966), regulation of gene expression (GO:0010468), regulation of cell migration (GO:0030334), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (17): protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), ATP binding (GO:0005524), activin receptor activity, type I (GO:0016361), activin receptor activity (GO:0017002), ubiquitin protein ligase binding (GO:0031625), inhibin binding (GO:0034711), SMAD binding (GO:0046332), metal ion binding (GO:0046872), activin binding (GO:0048185), I-SMAD binding (GO:0070411), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), growth factor binding (GO:0019838)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), signaling receptor complex (GO:0043235), activin receptor complex (GO:0048179), membrane (GO:0016020), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Developmental Biology	1
Signaling by NODAL	1
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	3
activin receptor signaling pathway	3
protein binding	3
gene expression	2
protein phosphorylation	2
negative regulation of cellular process	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
chordate embryonic development	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
system development	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
peptidyl-threonine modification	1
ossification	1
regulation of ossification	1
negative regulation of multicellular organismal process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
transforming growth factor beta receptor superfamily signaling pathway	1
regulation of activin receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cell differentiation	1
regulation of cell differentiation	1
negative regulation of developmental process	1
erythrocyte differentiation	1
positive regulation of myeloid cell differentiation	1

Protein interactions and networks

STRING

2192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACVR1B	MSTN	O14793	995
ACVR1B	CRIPTO	P13385	993
ACVR1B	ACVR2A	P27037	988
ACVR1B	ACVR2B	Q13705	988
ACVR1B	TGFBR1	P36897	975
ACVR1B	ALK	Q9UM73	929
ACVR1B	GDF11	O95390	926
ACVR1B	SMAD2	Q15796	921
ACVR1B	SMAD4	Q13485	911
ACVR1B	ACVR1C	Q8NER5	872
ACVR1B	ACVR1	Q04771	820
ACVR1B	INHBA	P08476	814
ACVR1B	SMAD3	P84022	813
ACVR1B	NODAL	Q96S42	802
ACVR1B	CFC1	P0CG37	789

IntAct

107 interactions, top by confidence:

A	B	Type	Score
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
ACVR1B	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
SMAD7	ACVR1B	psi-mi:“MI:0915”(physical association)	0.520
ACVR1B	SMAD7	psi-mi:“MI:0915”(physical association)	0.520
FKBP1A	ACVR1B	psi-mi:“MI:0915”(physical association)	0.510
ACVR1B	FKBP1A	psi-mi:“MI:0915”(physical association)	0.510
Acvr2b	ACVR1B	psi-mi:“MI:0914”(association)	0.500
ACVR1B	Acvr2b	psi-mi:“MI:0915”(physical association)	0.500
SMAD4	ACVR1B	psi-mi:“MI:2364”(proximity)	0.470
SMAD4	ACVR1B	psi-mi:“MI:0915”(physical association)	0.470
ACVR1B	PRKACB	psi-mi:“MI:0915”(physical association)	0.370
OS9	ACVR1B	psi-mi:“MI:0915”(physical association)	0.370
RXRA	ACVR1B	psi-mi:“MI:0915”(physical association)	0.370
BAG6	ACVR1B	psi-mi:“MI:0915”(physical association)	0.370
ACVR1B		psi-mi:“MI:0915”(physical association)	0.370
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
ndr1	Acvr2b	psi-mi:“MI:0914”(association)	0.350
Acvr2b	ndr1	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350

BioGRID (134): Dok1 (Affinity Capture-Western), ACVR2A (Affinity Capture-Western), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), OTUB1 (Biochemical Activity), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ACVR1B (Affinity Capture-MS)

ESM2 similar proteins: O00238, O08680, O42127, O42422, O46680, O73875, P09759, P22182, P29318, P29319, P29320, P29323, P36894, P36895, P36896, P36897, P36898, P37023, P37172, P54755, P54756, P54757, P54758, P54759, P54762, P70539, P80201, P80202, P80203, P80204, Q04771, Q05438, Q09488, Q15375, Q28041, Q5CD18, Q5RAN0, Q60629, Q61271, Q61288

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
“SB 505124”	down-regulates	ACVR1B	“chemical inhibition”
ACVR2B	“up-regulates activity”	ACVR1B	phosphorylation
ACVR1B	“up-regulates quantity by stabilization”	HBB
ACVR1B	“up-regulates quantity by stabilization”	HBA1
TDGF1	“up-regulates activity”	ACVR1B	binding
NODAL	“up-regulates activity”	ACVR1B	binding
ACVR1B	“up-regulates activity”	SMAD2	phosphorylation
ACVR1B	“up-regulates activity”	TDP2	phosphorylation
ACVR2A	up-regulates	ACVR1B	phosphorylation
ACVR1B	“up-regulates activity”	SMAD3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by TGFB family members	7	10.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
activin receptor signaling pathway	6	51.7×	1e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — BRCA, COAD, COADREAD, LUAD, PAAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	40
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1174607	NM_004302.5(ACVR1B):c.912G>A (p.Met304Ile)	Pathogenic
153751	GRCh38/hg38 12q13.12-13.13(chr12:50122359-53248460)x1	Pathogenic
8227	NM_004302.5(ACVR1B):c.1159_1163del (p.Asp387fs)	Pathogenic
8228	NM_004302.5(ACVR1B):c.1262-502_1392+24del	Pathogenic

SpliceAI

1638 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51975253:A:AG	acceptor_gain	1.0000
12:51975254:A:G	acceptor_gain	1.0000
12:51975262:CAGCT:C	acceptor_loss	1.0000
12:51975263:A:AG	acceptor_gain	1.0000
12:51975264:G:GT	acceptor_gain	1.0000
12:51975264:GCT:G	acceptor_gain	1.0000
12:51975264:GCTC:G	acceptor_gain	1.0000
12:51975264:GCTCT:G	acceptor_gain	1.0000
12:51975497:GCCC:G	donor_gain	1.0000
12:51975502:GTG:G	donor_gain	1.0000
12:51975505:G:GA	donor_loss	1.0000
12:51975505:G:GG	donor_gain	1.0000
12:51975506:T:A	donor_loss	1.0000
12:51976316:A:AG	acceptor_gain	1.0000
12:51976316:ACTT:A	acceptor_gain	1.0000
12:51976317:C:G	acceptor_gain	1.0000
12:51976319:T:TA	acceptor_gain	1.0000
12:51976323:TCAG:T	acceptor_loss	1.0000
12:51976325:A:AG	acceptor_gain	1.0000
12:51976326:G:GG	acceptor_gain	1.0000
12:51986816:A:AG	acceptor_gain	1.0000
12:51986817:G:GG	acceptor_gain	1.0000
12:51986940:G:GT	donor_gain	1.0000
12:51991858:CCCAG:C	acceptor_loss	1.0000
12:51991861:A:AC	acceptor_loss	1.0000
12:51991861:A:AG	acceptor_gain	1.0000
12:51991861:AG:A	acceptor_gain	1.0000
12:51991862:G:GG	acceptor_gain	1.0000
12:51991862:GG:G	acceptor_gain	1.0000
12:51991862:GGA:G	acceptor_gain	1.0000

AlphaMissense

3306 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51975327:T:A	C52S	1.000
12:51975327:T:C	C52R	1.000
12:51975328:G:A	C52Y	1.000
12:51975328:G:C	C52S	1.000
12:51975329:C:G	C52W	1.000
12:51975378:T:A	C69S	1.000
12:51975378:T:C	C69R	1.000
12:51975379:G:A	C69Y	1.000
12:51975379:G:C	C69S	1.000
12:51975380:C:G	C69W	1.000
12:51975423:T:A	C84S	1.000
12:51975423:T:C	C84R	1.000
12:51975424:G:A	C84Y	1.000
12:51975424:G:C	C84S	1.000
12:51975425:C:G	C84W	1.000
12:51975456:T:A	C95S	1.000
12:51975456:T:C	C95R	1.000
12:51975457:G:C	C95S	1.000
12:51975460:G:A	C96Y	1.000
12:51975461:C:G	C96W	1.000
12:51975474:T:A	C101S	1.000
12:51975475:G:A	C101Y	1.000
12:51975475:G:C	C101S	1.000
12:51975476:C:G	C101W	1.000
12:51975479:C:A	N102K	1.000
12:51975479:C:G	N102K	1.000
12:51980993:C:T	T202I	1.000
12:51980999:C:A	A204D	1.000
12:51981002:G:C	R205P	1.000
12:51981008:T:A	I207N	1.000

dbSNP variants (sampled 300 via entrez): RS1000113574 (12:51960291 G>A), RS1000129374 (12:51996883 C>T), RS1000204308 (12:51955057 G>C), RS1000207428 (12:51969009 G>C), RS1000312692 (12:51972445 G>A), RS1000398477 (12:51980316 C>T), RS1000467648 (12:51965033 A>G), RS1000468371 (12:51952343 G>A,T), RS1000543407 (12:51965635 G>A,C), RS1000633244 (12:51964588 A>G), RS1000731302 (12:51978448 A>G), RS1000890762 (12:51970624 G>A), RS1000914474 (12:51995255 G>GGTGGT), RS1001108936 (12:51985065 T>C), RS1001187544 (12:51990827 C>T)

Disease associations

OMIM: gene MIM:601300 | disease phenotypes: MIM:608808

GenCC curated gene-disease

Disease	Classification	Inheritance
malignant pancreatic neoplasm	No Known Disease Relationship	Unknown

Mondo (3): dextro-looped transposition of the great arteries (MONDO:0019443), exocrine pancreatic carcinoma (MONDO:0005192), malignant pancreatic neoplasm (MONDO:0009831)

Orphanet (3): Congenitally uncorrected transposition of the great arteries (Orphanet:860), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0002894	Neoplasm of the pancreas
HP:0003581	Adult onset
HP:0410067	Increased level of L-fucose in urine

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001791_24	Urate levels	2.000000e-09
GCST002491_14	Age-related hearing impairment	5.000000e-07
GCST003264_1439	Post bronchodilator FEV1/FVC ratio	3.000000e-07
GCST003264_1471	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003325_3	Lung cancer	5.000000e-09
GCST003326_3	Adenocarcinoma	2.000000e-09
GCST004613_29	Sum neutrophil eosinophil counts	2.000000e-11
GCST004614_7	Granulocyte count	2.000000e-11
GCST004620_127	Sum basophil neutrophil counts	3.000000e-11
GCST004629_102	Neutrophil count	2.000000e-11
GCST005994_12	Hematocrit	9.000000e-10
GCST005995_3	Hemoglobin	9.000000e-12
GCST011456_6	Serum CC16 levels	2.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004713	FEV/FVC ratio
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0005080	CC16 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5310 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 65,103 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL2364611	GALUNISERTIB	2	1,929
CHEMBL253969	OSI-632	2	1,150
CHEMBL3120215	OSI-027	2	1,854
CHEMBL3260567	VACTOSERTIB	2	898
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL5956963	KER-047	2	16
CHEMBL1090479	GSK-1070916	1	177
CHEMBL3600873	MK-5108	1	14
CHEMBL482967	CYC-116	1	651
CHEMBL5095192	PF-06952229	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type I receptor serine/threonine kinases

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
vactosertib	Inhibition	7.89	pIC50
BMS-986260	Inhibition	7.48	pIC50
galunisertib	Inhibition	7.11	pIC50
compound 13r [PMID: 23639540]	Inhibition	6.74	pIC50
compound 13d [PMID: 23639540]	Inhibition	6.49	pIC50

Binding affinities (BindingDB)

56 measured of 82 human assays (82 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
4-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	7.7 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	8 nM	US-9682983: BMP inhibitors and methods of use thereof
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
4-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	10 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	12 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[4-(4-fluorophenyl)-2-(4-methanesulfinylphenyl)-1H-imidazol-5-yl]pyridine	KD	12 nM
5-[6-[6-(2-piperazin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	14 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	15 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(5-piperazin-1-yl-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	16 nM	US-9682983: BMP inhibitors and methods of use thereof
5-piperazin-1-yl-2-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)-1,3-thiazole	IC50	19 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-[(2S,6R)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	22 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-(2-piperazin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	22 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(4-piperidin-4-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	23 nM	US-9682983: BMP inhibitors and methods of use thereof
2-chloro-4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	24 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxamide	IC50	26 nM	US-9682983: BMP inhibitors and methods of use thereof
BMS-354825	KD	27 nM
4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	29 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	30 nM	US-9682983: BMP inhibitors and methods of use thereof
US10017516, Compound 28	IC50	31 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-fluoro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylquinoline	IC50	32 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	38 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-4-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	43 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-amine	IC50	44 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-(3-chloro-4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	46 nM	US-9682983: BMP inhibitors and methods of use thereof
2-piperazin-1-yl-5-(3-quinolin-5-ylpyrazolo[1,5-a]pyrimidin-6-yl)benzonitrile	IC50	47 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[6-[(2R,6S)-2,6-dimethylpiperazin-1-yl]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	56 nM	US-9682983: BMP inhibitors and methods of use thereof
[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-8-yl]methanol	IC50	62 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(3-piperazin-1-ylprop-1-ynyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	68 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	85 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-[(3S)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	102 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(2-piperazin-1-ylpyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	103 nM	US-9682983: BMP inhibitors and methods of use thereof
N-[4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinolin-7-yl]acetamide	IC50	105 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxyphenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	106 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	107 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-[6-[2-(4-methylpiperazin-1-yl)ethoxy]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	122 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-7-carboxamide	IC50	127 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-[5-(1-methylpiperidin-4-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	155 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[4-[(2R,6S)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methoxyquinoline	IC50	157 nM	US-9682983: BMP inhibitors and methods of use thereof
2-methyl-5-[6-(5-piperidin-4-yloxy-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	180 nM	US-9682983: BMP inhibitors and methods of use thereof
4-(4-(benzo[d][1,3]dioxol-5-yl)-5-(pyridin-2-yl)-1H-imidazol-2-yl)benzamide	KD	190 nM
2-methyl-5-[6-[5-[(3R)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	276 nM	US-9682983: BMP inhibitors and methods of use thereof
4-[6-(4-piperidin-4-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	677 nM	US-9682983: BMP inhibitors and methods of use thereof
2-(5-chloro-2-fluorophenyl)-5-(propan-2-yl)-N-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}pyridin-4-amine	IC50	5450 nM	US-10030004: Compounds and methods of use
2-(5-chloro-2-fluorophenyl)-5-cyclopropyl-N-{1H-pyrrolo[2,3-b]pyridin-4-yl}pyridin-4-amine	IC50	5840 nM	US-10030004: Compounds and methods of use
2-(5-chloro-2-fluorophenyl)-5-(propan-2-yl)-N-{1H-pyrazolo[3,4-d]pyrimidin-4-yl}pyridin-4-amine	IC50	8930 nM	US-10030004: Compounds and methods of use
(S)-4-(2-(5-chloro-2-fluorophenyl)-5-isopropylpyridin-4-ylamino)-N-(2-hydroxypropyl)pyrimidine-5-carboxamide	IC50	9970 nM	US-10030004: Compounds and methods of use

ChEMBL bioactivities

253 potent at pChembl≥5 of 300 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	CHEMBL400402
8.68	IC50	2.1	nM	CHEMBL5591770
8.57	IC50	2.7	nM	CHEMBL5897331
8.43	IC50	3.7	nM	CHEMBL5813038
8.43	IC50	3.7	nM	CHEMBL5903130
8.40	Kd	4	nM	OSI-632
8.33	IC50	4.7	nM	CHEMBL5595138
8.32	IC50	4.8	nM	CHEMBL5818729
8.07	IC50	8.6	nM	CHEMBL5288333
8.00	IC50	10	nM	VACTOSERTIB
8.00	Kd	10	nM	CHEMBL1908395
7.98	IC50	10.5	nM	CHEMBL5818096
7.96	IC50	11	nM	CHEMBL6036046
7.94	IC50	11.5	nM	CHEMBL5995233
7.93	IC50	11.7	nM	CHEMBL5290769
7.89	IC50	13	nM	VACTOSERTIB
7.89	IC50	13	nM	CHEMBL4548795
7.89	IC50	13	nM	CHEMBL5922079
7.89	IC50	13	nM	CHEMBL5983777
7.80	Kd	16	nM	GALUNISERTIB
7.76	IC50	17.2	nM	VACTOSERTIB
7.75	IC50	18	nM	CHEMBL1829511
7.64	IC50	23	nM	CHEMBL492634
7.63	IC50	23.5	nM	CHEMBL6025407
7.62	IC50	23.7	nM	CHEMBL5800993
7.60	Kd	25.14	nM	CHEMBL5653589
7.60	IC50	25	nM	CHEMBL5989551
7.57	IC50	27	nM	CHEMBL5083143
7.52	IC50	30.4	nM	CHEMBL5768318
7.51	IC50	31	nM	CHEMBL3818173
7.50	IC50	31.5	nM	CHEMBL5957596
7.49	IC50	32.5	nM	CHEMBL5289691
7.48	IC50	33.1	nM	CHEMBL5791864
7.48	IC50	33.1	nM	CHEMBL5749427
7.46	IC50	34.6	nM	CHEMBL6172244
7.40	IC50	40.1	nM	CHEMBL5761663
7.40	IC50	40.2	nM	CHEMBL5972400
7.37	IC50	42.4	nM	CHEMBL5768693
7.36	IC50	43.29	nM	CHEMBL513147
7.35	IC50	45.1	nM	CHEMBL5285430
7.34	IC50	46	nM	CHEMBL424676
7.25	IC50	56.7	nM	PF-06952229
7.24	IC50	57	nM	PF-06952229
7.24	Kd	58	nM	CHEMBL1241674
7.23	IC50	59	nM	CHEMBL2024684
7.23	ED50	59.12	nM	CHEMBL5653589
7.16	IC50	70	nM	CHEMBL226838
7.12	Kd	75.42	nM	CHEMBL3752910
7.07	Kd	86	nM	LESTAURTINIB
7.06	IC50	86.8	nM	CHEMBL5857202

PubChem BioAssay actives

94 with measured affinity, of 1101 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
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-methoxy-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112254: Inhibition of ALK4 (unknown origin) by TR-FRET assay	ic50	0.0021	uM
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0040	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-[3-(hydroxymethyl)-4-pyridinyl]pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112254: Inhibition of ALK4 (unknown origin) by TR-FRET assay	ic50	0.0047	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624943: Binding constant for ACVR1B kinase domain	kd	0.0100	uM
2-fluoro-N-[[5-(6-methyl-2-pyridinyl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1H-imidazol-2-yl]methyl]aniline	1142609: Inhibition of ALK4 (unknown origin) by radioisotopic assay	ic50	0.0130	uM
4-[2-(6-methyl-2-pyridinyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0160	uM
N,N-dimethyl-3-[[5-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)-2-pyridinyl]-2-pyridinyl]oxy]propan-1-amine	618730: Inhibition of Activin A in human HEK293 cells transfected with luciferase and FAST-2 gene expression vector A3-LUX after 16 hrs by luciferase reporter gene assay	ic50	0.0180	uM
3-[[5-(6-methyl-2-pyridinyl)-4-quinoxalin-6-yl-1H-imidazol-2-yl]methyl]benzamide	1142609: Inhibition of ALK4 (unknown origin) by radioisotopic assay	ic50	0.0230	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147801: Binding affinity to human ACVR1B incubated for 45 mins by Kinobead based pull down assay	kd	0.0251	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1431778: Inhibition of human ALK4 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	ic50	0.0433	uM
N,N-dimethyl-2-[4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)-2-pyridinyl]phenoxy]ethanamine	618730: Inhibition of Activin A in human HEK293 cells transfected with luciferase and FAST-2 gene expression vector A3-LUX after 16 hrs by luciferase reporter gene assay	ic50	0.0460	uM
4-[[2-(5-chloro-2-fluorophenyl)-5-propan-2-yl-4-pyridinyl]amino]-N-(1,3-dihydroxypropan-2-yl)pyridine-3-carboxamide	1921886: Inhibition of ALK4 (unknown origin)	ic50	0.0570	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624943: Binding constant for ACVR1B kinase domain	kd	0.0580	uM
3-methyl-6-[2-(6-methyl-2-pyridinyl)pyrazol-3-yl]quinazolin-4-one	658824: Inhibition of ALK4	ic50	0.0590	uM
2-[4-(1,3-benzodioxol-5-yl)-2-tert-butyl-1H-imidazol-5-yl]-6-methylpyridine	1142609: Inhibition of ALK4 (unknown origin) by radioisotopic assay	ic50	0.0700	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147801: Binding affinity to human ACVR1B incubated for 45 mins by Kinobead based pull down assay	kd	0.0754	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507820: Binding affinity to ACVR1B	kd	0.0860	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624943: Binding constant for ACVR1B kinase domain	kd	0.0960	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624943: Binding constant for ACVR1B kinase domain	kd	0.0970	uM
N-[4-[3-[5-(trideuteriomethoxy)-2-pyridinyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423813: Inhibition of ALK4 (unknown origin)	ic50	0.1000	uM
N-[4-[3-[6-(difluoromethyl)-2-pyridinyl]-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridinyl]acetamide	1423813: Inhibition of ALK4 (unknown origin)	ic50	0.1000	uM
1-methyl-4-[5-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)-2-pyridinyl]-2-pyridinyl]piperazine	618730: Inhibition of Activin A in human HEK293 cells transfected with luciferase and FAST-2 gene expression vector A3-LUX after 16 hrs by luciferase reporter gene assay	ic50	0.1080	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1420	uM
4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzoic acid	1758206: Inhibition of human ALK4 using ATP as substrate incubated for 60 mins by ADP-glo based luminescence assay	ic50	0.1580	uM
4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637051: Inhibition of recombinant human GST-tagged ALK4 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.1700	uM
4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750129: Inhibition of ALK4 (unknown origin)	ic50	0.1830	uM
4-[4-(1,3-benzodioxol-5-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide	435898: Binding constant for ACVR1B kinase domain	kd	0.1900	uM
2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722085: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.1920	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1950	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637051: Inhibition of recombinant human GST-tagged ALK4 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.2000	uM
2-(1-methylpyrazol-4-yl)-4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridine	618730: Inhibition of Activin A in human HEK293 cells transfected with luciferase and FAST-2 gene expression vector A3-LUX after 16 hrs by luciferase reporter gene assay	ic50	0.2240	uM
3-(4-piperazin-1-ylphenyl)-5-(3,4,5-trimethoxyphenyl)pyridine-4-carbonitrile	1665311: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.2570	uM
3-(2-methylquinolin-4-yl)-6-(4-piperazin-1-ylphenyl)furo[3,2-b]pyridine	2113167: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.2860	uM
4-[4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]morpholine	750129: Inhibition of ALK4 (unknown origin)	ic50	0.3260	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435898: Binding constant for ACVR1B kinase domain	kd	0.3300	uM
6-(4-piperazin-1-ylphenyl)-3-[2-(trifluoromethyl)quinolin-4-yl]furo[3,2-b]pyridine	2113167: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.3860	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722085: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.3900	uM
1-[4-[5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine	1665311: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.4620	uM
2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722085: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.4640	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5240	uM
4-[4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5490	uM
6-fluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722085: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.5687	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722085: Inhibition of human ALK4 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.5961	uM
Dabrafenib	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.6010	uM
1-[4-[4-fluoro-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine	1665311: Inhibition of human ALK4 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.6300	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	435898: Binding constant for ACVR1B kinase domain	kd	0.6800	uM
2,5-dimethyl-6-quinolin-4-yl-3H-quinazolin-4-one	1399005: Binding affinity to human ALK4 by KdELECT assay	kd	0.6900	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637051: Inhibition of recombinant human GST-tagged ALK4 catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.7300	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1424901: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.7670	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases expression, affects reaction, increases abundance, increases phosphorylation	2
Cadmium Chloride	increases phosphorylation, increases expression, affects reaction, increases abundance	2
Particulate Matter	increases expression	2
bufotalin	increases expression	1
arsenite	increases methylation	1
nickel sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
imeglimin	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Ethanol	increases expression	1
Amiodarone	increases expression	1
Arsenic	affects expression	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases methylation	1
Carbamazepine	affects expression	1
Diclofenac	affects expression	1
Dust	decreases expression	1
Ethinyl Estradiol	decreases expression	1
Naled	affects expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Tacrolimus	affects binding, decreases reaction, decreases ubiquitination, decreases activity, increases reaction	1
Uranium Compounds	decreases expression	1

ChEMBL screening assays

286 unique, capped per target: 282 binding, 3 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032239	Binding	Inhibition of ACVR1B at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL3998848	ADMET	Inhibition of human ALK4 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277. — J Med Chem
CHEMBL5445953	Functional	Affinity Phenotypic Cellular interaction: (Western Blot (TGFxcexb2-induced phosphorylation of Smad3 in 4T1 cells)) EUB0000041b ACVR1B	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9WJ	CTSC#18	Cancer cell line	Female
CVCL_A9WW	CTSC#446	Cancer cell line	Female
CVCL_B8AU	Abcam HCT 116 ACVR1B KO	Cancer cell line	Male
CVCL_B8S5	Abcam MCF-7 ACVR1B KO	Cancer cell line	Female
CVCL_B9CW	Abcam A-549 ACVR1B KO	Cancer cell line	Male
CVCL_B9WA	Abcam THP-1 ACVR1B KO	Cancer cell line	Male
CVCL_D8H2	Ubigene HCT 116 ACVR1B KO	Cancer cell line	Male
CVCL_SB32	HAP1 ACVR1B (-)	Cancer cell line	Male
CVCL_ZG09	CLC48	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
NCT05245877	PHASE4	RECRUITING	Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery
NCT05784311	PHASE4	RECRUITING	Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
NCT06316908	PHASE4	COMPLETED	Permanent Celiac Plexus Block: Comparison of Pain Score in Unilateral and Bilateral Posterior Percutaneous Approach
NCT06779318	PHASE4	NOT_YET_RECRUITING	Maintenance Chemotherapy With S-1 vs. Observation After Adjuvant Therapy for Resected Pancreatic Cancer With High Risk of Recurrence/Metastasis
NCT07557394	PHASE4	NOT_YET_RECRUITING	A Prospective Non-randomized Controlled Interventional Study on the Effect of Shouhui Tongbian Capsules Combined With Pancreatin Enteric-coated Capsules on Pancreatic Exocrine Function in Patients After Curative Resection for Pancreatic Cancer
NCT00003029	PHASE3	COMPLETED	Fluorouracil With or Without Cisplatin in Treating Patients With Advanced or Metastatic Cancer of the Pancreas
NCT00003049	PHASE3	COMPLETED	Surgery Followed by Radiation Therapy and Chemotherapy in Treating Patients With Cancer of the Pancreas
NCT00003216	PHASE3	COMPLETED	Fluorouracil, Gemcitabine, and Radiation Therapy in Treating Patients With Cancer of the Pancreas
NCT00005869	PHASE3	UNKNOWN	Nitrocamptothecin Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced or Metastatic Pancreatic Cancer
NCT00005870	PHASE3	UNKNOWN	Nitrocamptothecin Compared With Other Chemotherapy in Treating Patients With Recurrent or Refractory Cancer of the Pancreas
NCT00005871	PHASE3	UNKNOWN	Nitrocamptothecin or Fluorouracil in Treating Patients With Recurrent or Refractory Pancreatic Cancer
NCT00014651	PHASE3	TERMINATED	Vapreotide in Treating Patients Undergoing Elective Pancreatic Resection
NCT00023972	PHASE3	COMPLETED	Gemcitabine With or Without Exatecan Mesylate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
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