BMPR1B

Summary

BMPR1B (bone morphogenetic protein receptor type 1B, HGNC:1077) is a protein-coding gene on chromosome 4q22.3, encoding Bone morphogenetic protein receptor type-1B (O00238). On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.

This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 658 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brachydactyly type A2 (Definitive, GenCC) — +8 more curated relationships
• GWAS associations: 19
• Clinical variants (ClinVar): 457 total — 12 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 90
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001203

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1077
Approved symbol	BMPR1B
Name	bone morphogenetic protein receptor type 1B
Location	4q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ALK6, CDw293
Ensembl gene	ENSG00000138696
Ensembl biotype	protein_coding
OMIM	603248
Entrez	658

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000264568, ENST00000394931, ENST00000440890, ENST00000502683, ENST00000506363, ENST00000509540, ENST00000512312, ENST00000515059, ENST00000672698, ENST00000873511, ENST00000873512, ENST00000873513, ENST00000873514, ENST00000873515, ENST00000873516, ENST00000956988

RefSeq mRNA: 4 — MANE Select: NM_001203 NM_001203, NM_001256792, NM_001256793, NM_001256794

CCDS: CCDS3642, CCDS58919

Canonical transcript exons

ENST00000515059 — 13 exons

Exon	Start	End
ENSE00000461085	95115685	95115787
ENSE00000461088	95129862	95130054
ENSE00000733182	95152643	95152773
ENSE00000733194	95124983	95125121
ENSE00000733203	95114720	95114822
ENSE00000935354	95131215	95131512
ENSE00001236518	94996040	94996134
ENSE00001236522	94875831	94875900
ENSE00001236528	94757955	94758068
ENSE00002077316	95154548	95158448
ENSE00002111841	95123810	95123906
ENSE00002456394	95148748	95148923
ENSE00003894599	95104408	95104567

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 91.97.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7188 / max 114.8289, expressed in 719 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48946	1.3181	601
48951	0.3695	83
48958	0.2933	104
48950	0.1927	84
48952	0.1089	54
48954	0.0866	50
48957	0.0742	47
48962	0.0639	29
48953	0.0591	43
48956	0.0562	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	91.97	gold quality
bronchial epithelial cell	CL:0002328	91.88	gold quality
cauda epididymis	UBERON:0004360	91.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.29	gold quality
buccal mucosa cell	CL:0002336	90.99	gold quality
seminal vesicle	UBERON:0000998	89.72	gold quality
entorhinal cortex	UBERON:0002728	87.60	gold quality
renal medulla	UBERON:0000362	87.44	gold quality
trigeminal ganglion	UBERON:0001675	86.70	gold quality
right uterine tube	UBERON:0001302	86.31	gold quality
lateral globus pallidus	UBERON:0002476	85.99	gold quality
medial globus pallidus	UBERON:0002477	85.03	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.93	gold quality
globus pallidus	UBERON:0001875	84.90	gold quality
dorsal root ganglion	UBERON:0000044	84.75	gold quality
ventricular zone	UBERON:0003053	84.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.98	gold quality
sural nerve	UBERON:0015488	83.71	gold quality
epithelium of bronchus	UBERON:0002031	83.54	gold quality
bronchus	UBERON:0002185	83.33	gold quality
corpus callosum	UBERON:0002336	83.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.10	gold quality
saphenous vein	UBERON:0007318	82.74	gold quality
superior vestibular nucleus	UBERON:0007227	82.68	gold quality
germinal epithelium of ovary	UBERON:0001304	82.63	gold quality
temporal lobe	UBERON:0001871	82.12	gold quality
postcentral gyrus	UBERON:0002581	81.89	gold quality
caudate nucleus	UBERON:0001873	81.79	gold quality
ventral tegmental area	UBERON:0002691	81.39	gold quality
parietal lobe	UBERON:0001872	81.30	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2188.28
E-GEOD-131882	yes	2005.29
E-MTAB-11268	yes	1051.53
E-MTAB-6108	yes	117.67
E-HCAD-35	yes	85.20
E-ANND-3	yes	15.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
BGLAP	Activation
HAMP	Activation
RUNX2	Activation
SP7	Activation

miRNA regulators (miRDB)

163 targeting BMPR1B, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-96-5P	99.95	72.80	2140

Literature-anchored findings (GeneRIF, showing 40)

• performed linkage analysis in brachydactyly (BD) type A2 and mapped a locus for BD type A2 to 4q21-q25. This interval includes the gene bone morphogenetic protein receptor 1B. (PMID:14523231)
• BMP-2-induced apoptosis was mediated by BMP-RIB in osteoblasts and occurred independently of BMP-2-induced osteoblast differentiation. (PMID:14576167)
• the BMP system is strongly involved in pulmonary artery smooth muscle mitosis through ALK-6, resulting in the progression of vascular remodeling of pulmonary arteries in pulmonary hypertension. (PMID:15192043)
• Anti mullerian hormnoe is a gonadal tumor suppressor which mediates its effects through a specific type II receptor and the bone morphogenetic protein (BMP)-specific Smad proteins. (PMID:15897891)
• GDF5 is a novel brachydactyly type A2 causing gene involving BMPR1b impaired activity. (PMID:16014698)
• Human granulosa-like tumor cell line KGN expressed BMP type I (BMPR1A and BMPR1B) and type II receptors (BMPR2) and the BMP signaling molecules SMADs (SMAD1 and SMAD5). (PMID:16436528)
• Results indicate that increased bone morphogenetic protein receptor (BMPR)-IB by TGF-beta1, FGF-2, and PDGF-AB significantly enhances BMP-2-induced osteogenesis in vitro. (PMID:17001689)
• HGF up-regulates the expression of the bone morphogenetic protein receptors, BMPR-IB and BMPR-II, in prostate cancer cells (PMID:17203235)
• significant shift in the emission maximum from 498 to 510 nm was detected when bis-ANS binds ecBMPR-IB. FRET revealed close proximity between the tyrosine & bis-ANS binding site. (PMID:17363346)
• Our results indicated the potential involvement of ALK6 activation by rhTGFbetas in the synergy between rhTGFbetas and rhBMPs. (PMID:17381068)
• Expression of BMP-4 and BMP-7 and their receptors in human ovaries from fetuses as well as adults. (PMID:17624341)
• there was significant down-regulation of ALK-6 (activin receptor-like kinase 6) expression in asthma patients at baseline; allergy challenge was associated with upregulation (PMID:18292470)
• Changes in BMPR1B localization regulate osteogenic responses of bone cells to BMP2. (PMID:18619554)
• Our study has provided evidence that BMPR-IB-dependent signaling plays a crucial role in BMP-2 up-regulation of the ALP, OC, Dlx5 and Cbfa1 genes in bone cells, suggesting a role of this receptor in BMP-2-induced osteoblast differentiation in vitro. (PMID:18773965)
• the interaction of Ror2 with BRIb is specific and independent of post-translational N-glycosylation. (PMID:19135982)
• decreased expression of BMPR-IB correlates with poor prognosis in breast cancer patients and leads to increased cell proliferation of breast cancer cells in vitro (PMID:19451094)
• Decrease BMPR-1B expression led to decreased SMAD1 phosphorylation and correlated witht he malignant grade of human gliomas and a poor prognosis. (PMID:19513897)
• Results suggest that allele-specific regulation of BMPR1B by miR-125b explains the observed disease risk in breast cancer. (PMID:19738052)
• Low BMP2 is associated with epithelial ovarian cancer. (PMID:20587070)
• Data show that blocking both endogenous BMPR1A and BMPR1B almost offset the effect of BMP7 on the proliferation of NCI-H460 cell completely. (PMID:20673479)
• BMPR1B were detected in the human retina and retinoblastoma cell lines. (PMID:21152263)
• rs1434536 in the 3’UTR of BMPR1B gene affects the binding ability of miR-125b to BMPR1B mRNA and contributes to the genetic predisposition to localized prostate cancer and patients aged>70 years. (PMID:21556765)
• generation of TGF-beta and BMP receptor homo- and hetero-oligomers and its roles as a mechanism capable of fast regulation of signaling by these crucial cytokines [review] (PMID:22293501)
• BMP15 uses preferentially BMPR1B as its type I receptor, suggesting an important role for the BMPR1B receptor in human female fertility (PMID:22294741)
• Suggest that BMPR1B mutations are associated with the pathogenesis of childhood idiopathic pulmonary arterial hypertension. (PMID:22374147)
• A significant association was observed between the 455C allele of BMP4 and increased left ventricular internal diameter systolic (p=0.004) and between 1650T allele of BMPR1B and lower left atrium diameter (p=0.038). (PMID:22971142)
• the shear-induced apoptosis and autophagy are mediated by bone morphogenetic protein receptor type (BMPR)-IB, BMPR-specific Smad1 and Smad5, and p38 mitogen-activated protein kinase. (PMID:24021264)
• Using primary cells and a cell line mimicking CP-CML, we found that myeloid progenitor expansion is driven by the exposure of immature cells overexpressing BMP receptor Ib to BMP2 and BMP4. (PMID:24100446)
• Data indicate missense (c.157T>C, p.(C53R)) or nonsense (c.657G>A, p.(W219*)) mutations in bone morphogenetic protein receptor type IB (BMPR1B) in two consanguineous families with acromesomelic chondrodysplasia-type Grebe. (PMID:24129431)
• Disrupting the binding of miR-125b toward BMPR1B would increase protein expression, diminishing abnormal cell proliferation as well as serum and cellular CA125 levels (PMID:24339876)
• Disequilibrium of BMP2 levels in the breast stem cell niche launches epithelial transformation by overamplifying BMPR1B cell response. (PMID:25601208)
• Two novel mutations in BMPR1B were identified in two patients with brachydactyly type A1. (PMID:25758993)
• Novel mutation in the BMPR1B gene (R486L) in a Polish family and further delineation of the phenotypic features of BMPR1B-related brachydactyly. (PMID:25776145)
• Data found a hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia (PMID:26105076)
• Using computational analyses with the COREX/BEST algorithm, the study uncovered an overall pattern connecting various regions of BMPR-1B ectodomain, including the four conserved residues in the protein-protein interface. (PMID:26562759)
• Low expression of BMPRIB is associated with breast cancer. (PMID:26684357)
• Data show that protein kinase LKB1 physically interacts with BMP type I receptors and requires Smad7 protein to promote downregulation of the receptor. (PMID:26701726)
• Results show an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density and suggest that the dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients. (PMID:26805635)
• Mutations in three genes (GDF5, NPR2, BMPR1B) have been reported to cause different forms of acromesomelic dysplasia (PMID:26926249)
• over-expression of CYP2J2 in MDA-MB-468-derived breast cancer cells activates BMPR1B expression that may contribute to increased migration (PMID:27720933)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmpr1bb	ENSDARG00000102742
danio_rerio	bmpr1ba	ENSDARG00000104100
mus_musculus	Bmpr1b	ENSMUSG00000052430
rattus_norvegicus	Bmpr1b	ENSRNOG00000016289
drosophila_melanogaster	tkv	FBGN0003716
caenorhabditis_elegans		WBGENE00004860

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR2B (ENSG00000114739), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Bone morphogenetic protein receptor type-1B — O00238 (reviewed: O00238)

All UniProt accessions (2): O00238, D6RGW8

UniProt curated annotations — full annotation on UniProt →

Function. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP7/OP-1 and GDF5. Positively regulates chondrocyte differentiation through GDF5 interaction.

Subunit / interactions. Interacts with high affinity with GDF5; positively regulates chondrocyte differentiation. Interacts with SCUBE3. Interacts with TSC22D1/TSC-22. Interacts with TGFBR3.

Subcellular location. Cell membrane.

Post-translational modifications. Autophosphorylated.

Disease relevance. Acromesomelic dysplasia 3 (AMD3) [MIM:609441] A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD3 is an autosomal recessive form characterized by bilateral aplasia of the fibula, severe brachydactyly, and fusion of carpal and tarsal bones. The disease is caused by variants affecting the gene represented in this entry. Brachydactyly A2 (BDA2) [MIM:112600] A form of brachydactyly. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. In brachydactyly type A2 shortening of the middle phalanges is confined to the index finger and the second toe, all other digits being more or less normal. Because of a rhomboid or triangular shape of the affected middle phalanx, the end of the second finger usually deviates radially. The disease is caused by variants affecting the gene represented in this entry. Brachydactyly A1, D (BDA1D) [MIM:616849] A form of brachydactyly type A1. Brachydactyly defines a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. BDA1D inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00238-1	1	yes
O00238-2	2

RefSeq proteins (4): NP_001194, NP_001243721, NP_001243722, NP_001243723 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_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: PF01064, PF07714, 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 (54 total): helix 16, sequence variant 11, strand 8, disulfide bond 5, binding site 2, topological domain 2, turn 2, domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3MDY	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00238-F1	85.36	0.61

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): 332 (proton acceptor)

Ligand- & substrate-binding residues (2): 231; 210–218

Disulfide bonds (5): 32–53, 34–38, 47–71, 81–95, 96–102

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 486 (showing top): YAATNRNNNYNATT_UNKNOWN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE, GOZGIT_ESR1_TARGETS_DN, GOBP_GROWTH, GOBP_OOGENESIS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, GOBP_CHONDROCYTE_DEVELOPMENT

GO Biological Process (32): MAPK cascade (GO:0000165), cartilage condensation (GO:0001502), ovarian cumulus expansion (GO:0001550), osteoblast differentiation (GO:0001649), eye development (GO:0001654), chondrocyte development (GO:0002063), inflammatory response (GO:0006954), dorsal/ventral pattern formation (GO:0009953), positive regulation of gene expression (GO:0010628), central nervous system neuron differentiation (GO:0021953), cell differentiation (GO:0030154), proteoglycan biosynthetic process (GO:0030166), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), retinal ganglion cell axon guidance (GO:0031290), positive regulation of chondrocyte differentiation (GO:0032332), ovulation cycle (GO:0042698), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of transcription by RNA polymerase II (GO:0045944), retina development in camera-type eye (GO:0060041), endochondral bone morphogenesis (GO:0060350), positive regulation of cartilage development (GO:0061036), cellular response to growth factor stimulus (GO:0071363), cellular response to BMP stimulus (GO:0071773), positive regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902043), negative regulation of chondrocyte proliferation (GO:1902731), chondrocyte differentiation (GO:0002062), protein phosphorylation (GO:0006468), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), camera-type eye development (GO:0043010), cartilage development (GO:0051216), bone development (GO:0060348)

GO Molecular Function (15): protein serine/threonine kinase activity (GO:0004674), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), transmembrane signaling receptor activity (GO:0004888), transforming growth factor beta receptor activity, type I (GO:0005025), ATP binding (GO:0005524), BMP binding (GO:0036122), SMAD binding (GO:0046332), metal ion binding (GO:0046872), BMP receptor activity (GO:0098821), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), signaling receptor activity (GO:0038023)

GO Cellular Component (6): plasma membrane (GO:0005886), dendrite (GO:0030425), neuronal cell body (GO:0043025), signaling receptor complex (GO:0043235), HFE-transferrin receptor complex (GO:1990712), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by TGFB family members	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chondrocyte differentiation	2
positive regulation of cell differentiation	2
intracellular signaling cassette	1
skeletal system morphogenesis	1
cartilage development	1
cell aggregation	1
antral ovarian follicle growth	1
ovulation cycle process	1
fused antrum stage	1
developmental growth	1
ossification	1
cell differentiation	1
sensory organ development	1
visual system development	1
cell development	1
defense response	1
regionalization	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
central nervous system development	1
neuron differentiation	1
cellular developmental process	1
proteoglycan metabolic process	1
glycoprotein biosynthetic process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
axon guidance	1
regulation of chondrocyte differentiation	1
positive regulation of cartilage development	1
rhythmic process	1
multicellular organismal reproductive process	1
osteoblast differentiation	1
regulation of osteoblast differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

26 interactions, top by confidence:

A	B	Type	Score
GDF5	BMPR1B	psi-mi:“MI:0407”(direct interaction)	0.680
BMPR1B	GDF5	psi-mi:“MI:0407”(direct interaction)	0.680
EVA1C	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
BMPR1B	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
BMPR1B	BMP2	psi-mi:“MI:0407”(direct interaction)	0.440
BMP2	BMPR1B	psi-mi:“MI:0407”(direct interaction)	0.440
BMPR1B	Lztr1	psi-mi:“MI:0915”(physical association)	0.400
Rhod	BMPR1B	psi-mi:“MI:0915”(physical association)	0.400
BMPR1B	Ubxn1	psi-mi:“MI:0915”(physical association)	0.400
BMPR1B	Rhebl1	psi-mi:“MI:0915”(physical association)	0.400
Fancl	BMPR1B	psi-mi:“MI:0915”(physical association)	0.400
BMPR1B	Plekhb1	psi-mi:“MI:0915”(physical association)	0.400
Chn1	BMPR1B	psi-mi:“MI:0915”(physical association)	0.400
BMPR1B	Sash3	psi-mi:“MI:0915”(physical association)	0.400
TPRA1	BMPR1B	psi-mi:“MI:0914”(association)	0.350
rep	BMPR1B	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): Nkiras1 (Affinity Capture-Luminescence), Rhebl1 (Affinity Capture-Luminescence), Rhod (Affinity Capture-Luminescence), Rab6b (Affinity Capture-Luminescence), Rab38 (Affinity Capture-Luminescence), Rhobtb1 (Affinity Capture-Luminescence), Rps27a (Affinity Capture-Luminescence), Fbxo3 (Affinity Capture-Luminescence), Sqstm1 (Affinity Capture-Luminescence), Dcaf7 (Affinity Capture-Luminescence), Mknk2 (Affinity Capture-Luminescence), Map2k3 (Affinity Capture-Luminescence), Fancl (Affinity Capture-Luminescence), Tgfbr1 (Affinity Capture-Luminescence), Lztr1 (Affinity Capture-Luminescence)

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

26 interactions.

A	Effect	B	Mechanism
AMHR2	up-regulates	BMPR1B	binding
BMPR2	up-regulates	BMPR1B	phosphorylation
BMPR1B	up-regulates	SMAD1	phosphorylation
BMPR1B	up-regulates	SMAD5	phosphorylation
BMPR1B	up-regulates	SMAD9	phosphorylation
NOG	“down-regulates activity”	BMPR1B	binding
BMPR1B	“up-regulates activity”	SMAD5	phosphorylation
BMPR1B	“up-regulates activity”	SMAD9	phosphorylation
BMPR1B	“up-regulates activity”	SMAD1	phosphorylation
BMPR1B	up-regulates	SMAD1/5/8	phosphorylation
BMPR1B	“form complex”	BMPR1A/1B/2	binding
BMPR1A	up-regulates	BMPR1B	binding
BMPR2	up-regulates	BMPR1B	binding
BMPR1B	up-regulates	SMAD1
BMPR1B	up-regulates	SMAD5
SMAD7	down-regulates	BMPR1B
GDF5	“up-regulates activity”	BMPR1B	binding
BMPR2	“up-regulates activity”	BMPR1B	binding
BMPR1B	“up-regulates activity”	STAMBP	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	8
Uncertain significance	221
Likely benign	105
Benign	69

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
217254	NM_001203.3(BMPR1B):c.157T>C (p.Cys53Arg)	Pathogenic
217255	NM_001203.3(BMPR1B):c.657G>A (p.Trp219Ter)	Pathogenic
217256	NM_001203.3(BMPR1B):c.91C>T (p.Arg31Cys)	Pathogenic
223155	NM_001203.3(BMPR1B):c.447-1G>A	Pathogenic
223156	NM_001203.3(BMPR1B):c.975A>C (p.Lys325Asn)	Pathogenic
2926869	NM_001203.3(BMPR1B):c.402_405del (p.Cys135fs)	Pathogenic
3246657	NC_000004.11:g.(?96025576)(96036958_?)del	Pathogenic
3752436	NM_001203.3(BMPR1B):c.1111C>T (p.Arg371Ter)	Pathogenic
4309267	NM_001203.3(BMPR1B):c.247-2A>G	Pathogenic
446284	NM_001203.3(BMPR1B):c.640C>A (p.Arg214Ser)	Pathogenic
6556	NM_001203.3(BMPR1B):c.1456C>T (p.Arg486Trp)	Pathogenic
6557	NM_001203.3(BMPR1B):c.361_368del (p.Gly121fs)	Pathogenic
2921762	NM_001203.3(BMPR1B):c.585+1G>C	Likely pathogenic
3065504	NM_001256793.2:c.-131339_868+386del	Likely pathogenic
384012	NM_001203.3(BMPR1B):c.1448C>T (p.Thr483Ile)	Likely pathogenic
6555	NM_001203.3(BMPR1B):c.599T>A (p.Ile200Lys)	Likely pathogenic
6558	NM_001203.3(BMPR1B):c.1457G>A (p.Arg486Gln)	Likely pathogenic
689613	NM_001203.3(BMPR1B):c.988C>T (p.His330Tyr)	Likely pathogenic
988503	NM_001203.3(BMPR1B):c.952_957del (p.Glu318_Ile319del)	Likely pathogenic
996696	NM_001203.3(BMPR1B):c.1190T>G (p.Met397Arg)	Likely pathogenic

SpliceAI

6203 predictions. Top by Δscore:

Variant	Effect	Δscore
4:94758065:GCGG:G	donor_gain	1.0000
4:94758068:GGTAA:G	donor_loss	1.0000
4:94758069:GTAA:G	donor_loss	1.0000
4:94758070:T:A	donor_loss	1.0000
4:94860331:G:GG	donor_gain	1.0000
4:94860339:T:G	donor_gain	1.0000
4:94875901:G:GA	donor_loss	1.0000
4:94875902:TAAG:T	donor_loss	1.0000
4:95079389:GGATA:G	donor_gain	1.0000
4:95104403:TTCA:T	acceptor_loss	1.0000
4:95104405:CA:C	acceptor_loss	1.0000
4:95104406:A:AG	acceptor_gain	1.0000
4:95104406:AGCA:A	acceptor_loss	1.0000
4:95104407:G:A	acceptor_loss	1.0000
4:95104407:G:GG	acceptor_gain	1.0000
4:95104407:GC:G	acceptor_gain	1.0000
4:95104407:GCA:G	acceptor_gain	1.0000
4:95104407:GCAA:G	acceptor_gain	1.0000
4:95104407:GCAAA:G	acceptor_gain	1.0000
4:95104563:TGCAG:T	donor_loss	1.0000
4:95104565:CAGGT:C	donor_loss	1.0000
4:95104566:AG:A	donor_loss	1.0000
4:95104567:GGTT:G	donor_loss	1.0000
4:95104569:T:A	donor_loss	1.0000
4:95115679:TTATA:T	acceptor_loss	1.0000
4:95115680:TATA:T	acceptor_loss	1.0000
4:95115681:ATAGG:A	acceptor_loss	1.0000
4:95115682:TAGG:T	acceptor_loss	1.0000
4:95115683:A:AG	acceptor_gain	1.0000
4:95115683:AGGAC:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10000023 (4:94812755 G>A,C,T), RS1000006632 (4:94757387 C>G), RS1000008098 (4:94760597 G>C), RS1000009617 (4:95045636 C>A,G), RS1000021046 (4:94878560 A>G,T), RS1000022322 (4:95131748 A>G), RS1000027242 (4:95070571 T>A,C), RS1000030039 (4:94847912 A>G), RS1000033206 (4:95005762 A>G), RS1000039185 (4:95001921 T>C,G), RS1000039575 (4:95070830 G>A), RS1000041655 (4:94926921 T>C), RS1000054128 (4:95031457 AT>A,ATT), RS1000054980 (4:95131994 C>G), RS1000057138 (4:94845444 G>A)

Disease associations

OMIM: gene MIM:603248 | disease phenotypes: MIM:112600, MIM:609441, MIM:616849, MIM:228900, MIM:615343, MIM:201250

GenCC curated gene-disease

Disease	Classification	Inheritance
brachydactyly type A2	Definitive	Autosomal recessive
acromesomelic dysplasia 3	Strong	Autosomal recessive
brachydactyly type A1D	Strong	Autosomal dominant
coloboma	Strong	Autosomal dominant
brachydactyly	Moderate	Autosomal dominant
pulmonary arterial hypertension	Moderate	Autosomal dominant
acromesomelic dysplasia 2A	Supportive	Autosomal recessive
acromesomelic dysplasia 2B	Supportive	Autosomal recessive
brachydactyly type A1	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pulmonary arterial hypertension	Disputed	UD

Mondo (13): brachydactyly type A2 (MONDO:0007216), acromesomelic dysplasia 3 (MONDO:0012274), brachydactyly type A1D (MONDO:0014798), brachydactyly (MONDO:0021004), pulmonary arterial hypertension (MONDO:0015924), acromesomelic dysplasia 2B (MONDO:0009231), pulmonary hypertension, primary, 3 (MONDO:0014135), premature menopause (MONDO:0001119), idiopathic pulmonary arterial hypertension (MONDO:0001999), acromesomelic dysplasia 2C, Hunter-Thompson type (MONDO:0008717), acromesomelic dysplasia 2A (MONDO:0008703), brachydactyly type A1 (MONDO:0007215), coloboma (MONDO:0001476)

Orphanet (8): Brachydactyly type A2 (Orphanet:93396), Brachydactyly type A1 (Orphanet:93388), Pulmonary arterial hypertension (Orphanet:182090), Fibular aplasia-complex brachydactyly syndrome (Orphanet:2639), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422), Pulmonary arterial hypertension associated with congenital heart disease (Orphanet:275803), Idiopathic pulmonary arterial hypertension (Orphanet:275766), Acromesomelic dysplasia, Hunter-Thompson type (Orphanet:968)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000446	Narrow nasal bridge
HP:0000750	Delayed speech and language development
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0001156	Brachydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001172	Abnormal thumb morphology
HP:0001204	Distal finger symphalangism
HP:0001230	Broad metacarpals
HP:0001231	Abnormal fingernail morphology
HP:0001376	Limitation of joint mobility
HP:0001387	Joint stiffness
HP:0001522	Death in infancy
HP:0001760	Abnormal foot morphology
HP:0001762	Talipes equinovarus
HP:0001769	Broad foot
HP:0001773	Short foot
HP:0001776	Bilateral talipes equinovarus
HP:0001822	Hallux valgus
HP:0001831	Short toe
HP:0002311	Incoordination
HP:0002650	Scoliosis
HP:0002652	Skeletal dysplasia
HP:0002750	Delayed skeletal maturation
HP:0002818	Abnormal morphology of the radius
HP:0002983	Micromelia
HP:0002990	Fibular aplasia

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000684_2	Attention deficit hyperactivity disorder	2.000000e-06
GCST002337_123	Amyotrophic lateral sclerosis (sporadic)	6.000000e-06
GCST004977_1	Hen’s egg allergy	7.000000e-07
GCST005194_233	Coronary artery disease	6.000000e-08
GCST006479_137	Diverticular disease	6.000000e-09
GCST006624_61	Systolic blood pressure	1.000000e-12
GCST006979_446	Heel bone mineral density	5.000000e-09
GCST007219_1	Schizophrenia	3.000000e-09
GCST007267_92	Systolic blood pressure	6.000000e-10
GCST007856_43	Colorectal cancer or advanced adenoma	1.000000e-08
GCST008155_10	Waist-hip ratio	7.000000e-06
GCST009313_1	Prepulse inhibition of the startle response	3.000000e-07
GCST010538_11	Sum of carotid plaque area	1.000000e-06
GCST010539_1	Sum of stenosis	2.000000e-07
GCST010541_1	Maximum stenosis	1.000000e-06
GCST010570_3	Polycystic ovary syndrome (reproductive subtype)	1.000000e-08
GCST010866_23	Coronary artery disease	6.000000e-10
GCST012222_3	Opioid dependence (time to event)	1.000000e-06
GCST90014033_31	Haemorrhoidal disease	5.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007018	egg allergy measurement
EFO:0009959	diverticular disease
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0004343	waist-hip ratio
EFO:0007969	cognitive inhibition measurement
EFO:0006501	carotid plaque build

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D059327	Brachydactyly	C05.660.585.262; C16.131.621.585.262
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C537088	Brachydactyly type A1 (supp.)
C537089	Brachydactyly type A2 (supp.)
C537913	Chondrodysplasia, acromesomelic, with genital anomalies (supp.)
C537931	Fibular hypoplasia and complex brachydactyly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5476 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 239,287 (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
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL5314579	ZILURGISERTIB	2	26
CHEMBL572878	TOZASERTIB	2
CHEMBL5956963	KER-047	2
CHEMBL1614725	TAK-285	1
CHEMBL1908397	KW-2449	1
CHEMBL259084	MLN-8054	1
CHEMBL3545085	XL-228	1
CHEMBL3545360	ASP-3026	1
CHEMBL551064	AEW-541	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
compound 13d [PMID: 23639540]	Inhibition	8.3	pIC50
compound 13r [PMID: 23639540]	Inhibition	8.3	pIC50
compound 13a [PMID: 23639540]	Inhibition	7.22	pIC50
galunisertib	Inhibition	6.33	pIC50
zilurgisertib	Inhibition	5.48	pIC50

Binding affinities (BindingDB)

58 measured of 58 human assays (58 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
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
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-(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-[6-[6-[2-(4-methylpiperazin-1-yl)ethoxy]-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	17 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
5-[6-[5-(2-methyl-1-piperidin-1-ylpropan-2-yl)oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	28 nM	US-9682983: BMP inhibitors and methods of use thereof
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-[5-[(3S)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	34 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
5-[6-(5-piperidin-4-yloxy-2-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	41 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
5-[6-[5-(1-methylpiperidin-4-yl)oxy-2-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-[5-[(3R)-pyrrolidin-3-yl]oxy-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	45 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
4-[6-[3-chloro-4-(2-piperidin-1-ylethoxy)phenyl]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
5-[6-[4-[(2S,6R)-2,6-dimethylpiperazin-1-yl]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-one	IC50	66 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
5-[6-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	84 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
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline-8-carboxylic acid	IC50	88 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-yl]methanol	IC50	102 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
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
5-[6-[6-(2-piperidin-1-ylethoxy)-3-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	127 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-[2-(4-methylpiperazin-1-yl)ethoxy]-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	151 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-[5-(2-piperidin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	157 nM	US-9682983: BMP inhibitors and methods of use thereof
5-[6-[5-(2-piperazin-1-ylethoxy)-2-pyridinyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	IC50	157 nM	US-10017516: 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
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

ChEMBL bioactivities

408 potent at pChembl≥5 of 452 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Kd	0.3	nM	CHEMBL5633837
9.07	Kd	0.85	nM	TAE-684
9.03	IC50	0.94	nM	CHEMBL513147
8.70	Kd	2	nM	CHEMBL3688339
8.68	Kd	2.1	nM	CHEMBL1241674
8.40	Kd	4	nM	CHEMBL386051
7.90	IC50	12.7	nM	CHEMBL513147
7.82	IC50	15	nM	CHEMBL5590317
7.82	IC50	15	nM	CHEMBL6033935
7.74	IC50	18.4	nM	CHEMBL4740381
7.72	Kd	19	nM	MOMELOTINIB
7.68	Kd	21	nM	AT-9283
7.66	IC50	22	nM	CHEMBL5989551
7.54	Kd	29	nM	SARACATINIB
7.53	IC50	29.4	nM	CHEMBL4788859
7.42	IC50	38	nM	CHEMBL5791901
7.41	Kd	39	nM	CHEMBL4247751
7.39	IC50	40.9	nM	CHEMBL4786529
7.39	IC50	41	nM	CHEMBL5083143
7.32	IC50	47.6	nM	CHEMBL2385597
7.30	EC50	50	nM	CHEMBL513147
7.29	IC50	51	nM	CHEMBL6027076
7.28	IC50	52	nM	CHEMBL6054748
7.28	Kd	53	nM	DASATINIB
7.26	IC50	54.5	nM	CHEMBL4742906
7.25	IC50	56.9	nM	CHEMBL511563
7.24	Kd	57	nM	LESTAURTINIB
7.22	IC50	60	nM	CHEMBL513147
7.21	IC50	60.9	nM	CHEMBL2385579
7.17	IC50	68	nM	CHEMBL4517408
7.08	IC50	82.4	nM	CHEMBL5591770
7.06	IC50	88	nM	CHEMBL4548795
7.03	IC50	92.9	nM	CHEMBL2385591
7.02	Kd	96	nM	CHEMBL4244382
6.99	IC50	102	nM	CHEMBL2385600
6.97	IC50	107	nM	MOMELOTINIB
6.97	IC50	106	nM	CHEMBL5915599
6.92	Kd	120	nM	KW-2449
6.91	Kd	123	nM	CHEMBL3991933
6.91	IC50	123	nM	CHEMBL5595157
6.89	IC50	129	nM	CHEMBL2385586
6.85	IC50	140	nM	CHEMBL5827469
6.82	IC50	150	nM	CHEMBL5954063
6.80	IC50	160	nM	CHEMBL5879231
6.77	Kd	170	nM	STAUROSPORINE
6.74	IC50	184	nM	CHEMBL6015579
6.73	IC50	188	nM	CHEMBL4778971
6.69	IC50	204	nM	CHEMBL5945070
6.67	Kd	212	nM	XL-228
6.67	IC50	213	nM	CHEMBL4280599

PubChem BioAssay actives

87 with measured affinity, of 514 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
2-[2-methyl-5-[3-(3,4,5-trimethoxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]anilino]ethanol	2137768: Binding affinity to human BMPR1B assessed as dissociation constant by Adp-glo assay	kd	0.0003	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	624825: Binding constant for BMPR1B kinase domain	kd	0.0008	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1431780: Inhibition of human ALK6 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	ic50	0.0009	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1424922: 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	0.0020	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624825: Binding constant for BMPR1B kinase domain	kd	0.0021	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624825: Binding constant for BMPR1B kinase domain	kd	0.0040	uM
4-[6-[4-(4-methylpiperazin-1-yl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0050	uM
4-[4-(3-quinolin-4-ylpyrazolo[1,5-a]pyrimidin-6-yl)phenyl]morpholine	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0050	uM
6-[4-(4-methylpiperazin-1-yl)phenyl]-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)furo[3,2-b]pyridine	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.0150	uM
2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722087: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0184	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1424922: 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	0.0210	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424922: 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	0.0290	uM
6-fluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722087: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0294	uM
2,5-dimethyl-6-quinolin-4-yl-3H-quinazolin-4-one	1399007: Binding affinity to human ALK6 by KdELECT assay	kd	0.0390	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-1-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722087: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0409	uM
6-(4-piperazin-1-ylphenyl)-3-quinolin-4-ylfuro[3,2-b]pyridine	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.0410	uM
4-[6-(4-propan-2-yloxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0476	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	624825: Binding constant for BMPR1B kinase domain	kd	0.0530	uM
2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722087: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0545	uM
4-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0569	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	507843: Binding affinity to BMPR1B	kd	0.0570	uM
4-[4-[3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0609	uM
1-[4-[4-methyl-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]piperazine	1665330: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay	ic50	0.0680	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-methoxy-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112255: Inhibition of ALK6 (unknown origin) by TR-FRET assay	ic50	0.0824	uM
2-fluoro-6-methoxy-4-[4-methyl-5-[4-(4-propan-2-ylpiperazin-1-yl)phenyl]-3-pyridinyl]benzamide	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.0880	uM
5-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	750128: Inhibition of ALK6 (unknown origin)	ic50	0.0929	uM
3-(4-morpholin-4-ylphenyl)-6-quinolin-4-ylquinazolin-4-one	1399007: Binding affinity to human ALK6 by KdELECT assay	kd	0.0960	uM
6-(4-methoxyphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750128: Inhibition of ALK6 (unknown origin)	ic50	0.1020	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624825: Binding constant for BMPR1B kinase domain	kd	0.1200	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1424922: 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	0.1230	uM
3-(2-methylquinolin-4-yl)-6-(4-piperazin-1-ylphenyl)furo[3,2-b]pyridine	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.1230	uM
6-(4-piperazin-1-ylphenyl)-3-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine	750128: Inhibition of ALK6 (unknown origin)	ic50	0.1290	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	624825: Binding constant for BMPR1B kinase domain	kd	0.1700	uM
6,8-difluoro-2-methyl-4-[7-(4-piperazin-2-ylphenyl)imidazo[1,2-a]pyridin-3-yl]quinoline	1722087: Inhibition of human ALK6 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.1880	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424922: 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	0.2120	uM
Crizotinib	624825: Binding constant for BMPR1B kinase domain	kd	0.2300	uM
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	1948597: Inhibition of ALK6 (unknown origin)	ic50	0.2350	uM
Vandetanib	624825: Binding constant for BMPR1B kinase domain	kd	0.2400	uM
6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin-4-amine	1673293: Binding affinity to human wild type partial length BMPR1B (D178 to L502 residues) expressed in mammalian expression system by Kinomescan method	kd	0.2800	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624825: Binding constant for BMPR1B kinase domain	kd	0.3700	uM
Fedratinib	624825: Binding constant for BMPR1B kinase domain	kd	0.4100	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624825: Binding constant for BMPR1B kinase domain	kd	0.4500	uM
N-methyl-3-[6-(4-piperazin-1-ylphenyl)furo[3,2-b]pyridin-3-yl]benzamide	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.5240	uM
4-[6-(4-piperazin-1-ylphenyl)furo[3,2-b]pyridin-3-yl]pyridin-2-amine	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.5320	uM
1-[4-[6-[4-(4-methylpiperazin-1-yl)phenyl]furo[3,2-b]pyridin-3-yl]-2-pyridinyl]ethanone	2113169: Inhibition of human ALK6 using casein as substrate in presence of [gamma-33P]ATP and 10 uM ATP by radiometric assay	ic50	0.5360	uM
Gilteritinib	1424922: 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	0.5720	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	624825: Binding constant for BMPR1B kinase domain	kd	0.7100	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624825: Binding constant for BMPR1B kinase domain	kd	0.7200	uM
4-quinolin-3-yl-1H-imidazo[4,5-c]pyridin-2-amine	693111: Binding affinity to BMPR1B	kd	0.7200	uM
(4S,9S,10S)-9,10,18-trihydroxy-16-methoxy-4-methyl-3-oxabicyclo[12.4.0]octadeca-1(14),15,17-triene-2,8-dione	1431780: Inhibition of human ALK6 using casein as substrate in presence of 10 uM ATP by radiometric kinase assay	ic50	0.7270	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	8
bisphenol A	affects localization, increases expression, increases methylation	3
Benzo(a)pyrene	affects localization, affects methylation	3
trichostatin A	decreases expression, increases expression	2
sodium arsenite	affects expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
dorsomorphin	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Silicon Dioxide	increases expression, decreases expression	2
Dihydrotestosterone	increases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
methyleugenol	decreases expression	1
butyraldehyde	decreases expression	1
rutecarpine	decreases expression	1
5,5’-bis(8-(phenylamino)-1-naphthalenesulfonate)	affects binding	1
9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine	increases expression	1
CGP 52608	affects binding, increases reaction	1
SU 9516	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
belinostat	decreases expression	1
enzalutamide	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases reaction, affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Panobinostat	affects expression, increases reaction	1
Glyphosate	decreases expression	1
Arbutin	decreases expression	1

ChEMBL screening assays

166 unique, capped per target: 164 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017878	Binding	Inhibition of BMPR1B assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem
CHEMBL3998850	ADMET	Inhibition of human ALK6 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

Cellosaurus cell lines

5 cell lines: 3 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9A7	Ubigene HEK293 BMPR1B KO	Transformed cell line	Female
CVCL_RQ02	C2C12-Bmpr1b	Spontaneously immortalized cell line	Female
CVCL_RQ03	C2C12-R486Q-Bmpr1b	Spontaneously immortalized cell line	Female
CVCL_RQ04	C2C12-R486W-Bmpr1b	Spontaneously immortalized cell line	Female
CVCL_SF40	HAP1 BMPR1B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
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