Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGKF90)

• DTT Name: Bone morphogenetic protein receptor (BMPR2)
• Synonyms: PPH1; Bone morphogenetic protein receptor type-2; Bone morphogenetic protein receptor type II; BMPR-II; BMPR-2; BMP type-2 receptor; BMP type II receptor
• Gene Name: BMPR2
• DTT Type: Literature-reported target; [1]
• Related Disease:
  Joint derangement [ICD-11: FA34]
  Prostate cancer [ICD-11: 2C82]
  Urinary system disease [ICD-11: GC2Z]
  Urinary/pelvic organs injury [ICD-11: NB92]
• BioChemical Class: Kinase
• UniProt ID: BMPR2_HUMAN
• TTD ID: T60213
• EC Number: EC 2.7.11.30
• Sequence:
  MTSSLQRPWRVPWLPWTILLVSTAAASQNQERLCAFKDPYQQDLGIGESRISHENGTILC
  SKGSTCYGLWEKSKGDINLVKQGCWSHIGDPQECHYEECVVTTTPPSIQNGTYRFCCCST
  DLCNVNFTENFPPPDTTPLSPPHSFNRDETIIIALASVSVLAVLIVALCFGYRMLTGDRK
  QGLHSMNMMEAAASEPSLDLDNLKLLELIGRGRYGAVYKGSLDERPVAVKVFSFANRQNF
  INEKNIYRVPLMEHDNIARFIVGDERVTADGRMEYLLVMEYYPNGSLCKYLSLHTSDWVS
  SCRLAHSVTRGLAYLHTELPRGDHYKPAISHRDLNSRNVLVKNDGTCVISDFGLSMRLTG
  NRLVRPGEEDNAAISEVGTIRYMAPEVLEGAVNLRDCESALKQVDMYALGLIYWEIFMRC
  TDLFPGESVPEYQMAFQTEVGNHPTFEDMQVLVSREKQRPKFPEAWKENSLAVRSLKETI
  EDCWDQDAEARLTAQCAEERMAELMMIWERNKSVSPTVNPMSTAMQNERNLSHNRRVPKI
  GPYPDYSSSSYIEDSIHHTDSIVKNISSEHSMSSTPLTIGEKNRNSINYERQQAQARIPS
  PETSVTSLSTNTTTTNTTGLTPSTGMTTISEMPYPDETNLHTTNVAQSIGPTPVCLQLTE
  EDLETNKLDPKEVDKNLKESSDENLMEHSLKQFSGPDPLSSTSSSLLYPLIKLAVEATGQ
  QDFTQTANGQACLIPDVLPTQIYPLPKQQNLPKRPTSLPLNTKNSTKEPRLKFGSKHKSN
  LKQVETGVAKMNTINAAEPHVVTVTMNGVAGRNHSVNSHAATTQYANGTVLSGQTTNIVT
  HRAQEMLQNQFIGEDTRLNINSSPDEHEPLLRREQQAGHDEGVLDRLVDRRERPLEGGRT
  NSNNNNSNPCSEQDVLAQGVPSTAADPGPSKPRRAQRPNSLDLSATNVLDGSSIQIGEST
  QDGKSGSGEKIKKRVKTPYSLKRWRPSTWVISTESLDCEVNNNGSNRAVHSKSSTAVYLA
  EGGTATTMVSKDIGMNCL
• Function: Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta signaling pathway (hsa04350)
  Hippo signaling pathway (hsa04390)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Signaling by BMP (R-HSA-201451)

Molecular Interaction Atlas (MIA) of This DTT

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AA-123	DMW73A8	Prostate cancer	2C82.0	Investigative	[1]
AA-166	DM2BMAZ	Articular cartilage disorder	FA34.Y	Investigative	[1]
AA-184	DMCN4ZD	Kidney injury	NB92.0	Investigative	[1]
AA-204	DMBGTX9	Kidney disease	GC2Z	Investigative	[1]
LDN-214117	DM57Z8J	Discovery agent	N.A.	Investigative	[2]
ML347	DMR8N36	Discovery agent	N.A.	Investigative	[3]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[3]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[3]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[3]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1794).
• [2] Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 2014 Oct 9;57(19):7900-15.
• [3] Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 2013 Jun 1;23(11):3248-52.