Target Information
| Target General Information | Top | |||||
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| Target ID |
T12091
(Former ID: TTDI03010)
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| Target Name |
Activin receptor-like kinase 2 (ALK-2)
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| 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
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| Gene Name |
ACVR1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Anemia [ICD-11: 3A00-3A9Z] | |||||
| 2 | Multiple myeloma [ICD-11: 2A83] | |||||
| 3 | Myelodysplastic syndrome [ICD-11: 2A37] | |||||
| 4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.30
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| Sequence |
MVDGVMILPVLIMIALPSPSMEDEKPKVNPKLYMCVCEGLSCGNEDHCEGQQCFSSLSIN
DGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNF HLEVGLIILSVVFAVCLLACLLGVALRKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTL ADLLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSR DEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTL DTVSCLRIVLSIASGLAHLHIEIFGTQGKPAIAHRDLKSKNILVKKNGQCCIADLGLAVM HSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVS NGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQ NPSARLTALRIKKTLTKIDNSLDKLKTDC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T97TLX | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | INCB00928 | Drug Info | Phase 2 | Multiple myeloma | [2] | |
| 2 | TP-0184 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 9 Inhibitor drugs | + | ||||
| 1 | INCB00928 | Drug Info | [4] | |||
| 2 | TP-0184 | Drug Info | [5] | |||
| 3 | PMID27774822-Compound-Figure10Compound12 | Drug Info | [1] | |||
| 4 | PMID27774822-Compound-Figure10Compound4 | Drug Info | [1] | |||
| 5 | LDN-214117 | Drug Info | [6] | |||
| 6 | ML347 | Drug Info | [7] | |||
| 7 | PMID23639540C13a | Drug Info | [7] | |||
| 8 | PMID23639540C13d | Drug Info | [7] | |||
| 9 | PMID23639540C13r | Drug Info | [7] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | ClinicalTrials.gov (NCT04582539) To Assess the Safety and Tolerability of INCB000928 in Participants With Myelodysplastic Syndromes or Multiple Myeloma.. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT03429218) First-in-human Study of Oral TP-0184 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of Incyte. | |||||
| REF 5 | Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma. | |||||
| REF 6 | 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. | |||||
| REF 7 | 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. | |||||
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