Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Activin receptor-like kinase 2 (ALK-2)
• Synonyms: TSR-I; TGF-B superfamily receptor type I; Serine/threonine-protein kinase receptor R1; SKR1; Activin receptor type-1; Activin receptor type I; ACVRLK2; ACTR-I
• Gene Name: ACVR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: ACVR1_HUMAN
• TTD ID: T12091
• EC Number: EC 2.7.11.30
• Sequence:
  MVDGVMILPVLIMIALPSPSMEDEKPKVNPKLYMCVCEGLSCGNEDHCEGQQCFSSLSIN
  DGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNF
  HLEVGLIILSVVFAVCLLACLLGVALRKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTL
  ADLLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSR
  DEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTL
  DTVSCLRIVLSIASGLAHLHIEIFGTQGKPAIAHRDLKSKNILVKKNGQCCIADLGLAVM
  HSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVS
  NGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQ
  NPSARLTALRIKKTLTKIDNSLDKLKTDC
• Function: Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved for left-right pattern formation during embryogenesis. 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)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Fluid shear stress and atherosclerosis (hsa05418)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
INCB00928	DMFG8TI	Anemia	3A00-3A9Z	Phase 2	[2]
TP-0184	DMJVZBC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27774822-Compound-Figure10Compound12	DMFAGOZ	N. A.	N. A.	Patented	[1]
PMID27774822-Compound-Figure10Compound4	DMMJVTW	N. A.	N. A.	Patented	[1]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LDN-214117	DM57Z8J	Discovery agent	N.A.	Investigative	[4]
ML347	DMR8N36	Discovery agent	N.A.	Investigative	[5]
PMID23639540C13a	DMLXOAQ	Discovery agent	N.A.	Investigative	[5]
PMID23639540C13d	DMSTQGH	Discovery agent	N.A.	Investigative	[5]
PMID23639540C13r	DMHBZ0N	Discovery agent	N.A.	Investigative	[5]

References

• [1] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2.Expert Opin Ther Pat. 2017 Feb;27(2):145-161.
• [2] Clinical pipeline report, company report or official report of Incyte.
• [3] Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
• [4] 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.
• [5] 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.