| Identification | Back Directory | [Name]
OTX015 | [CAS]
202590-98-5 | [Synonyms]
OTX015
MK8628
MK-8628
OTX-015
OTX 015
MK 8628
OTX015(OTX-015)
(S)-4-(4-Chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide
(6S)-4-(4-chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide
6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6S)-
(S)-4-(4-Chlorophenyl)-N-(4-hydroxyphenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide OTX-015 | [Molecular Formula]
C25H22ClN5O2S | [MDL Number]
MFCD26960949 | [MOL File]
202590-98-5.mol | [Molecular Weight]
491.992 |
| Chemical Properties | Back Directory | [Melting point ]
220 °C | [density ]
1.45±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
≥24.6 mg/mL in DMSO; insoluble in H2O; ≥106 mg/mL in EtOH with gentle warming | [form ]
powder | [pka]
10.05±0.26(Predicted) | [color ]
white to light brown | [InChIKey]
GNMUEVRJHCWKTO-FQEVSTJZSA-N | [SMILES]
N12C(C)=NN=C1[C@H](CC(NC1=CC=C(O)C=C1)=O)N=C(C1=CC=C(Cl)C=C1)C1C(C)=C(C)SC=12 |
| Questions And Answer | Back Directory | [Description]
OTX015 is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Phase 1. | [Features]
Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies. | [In vitro]
OTX015 inhibits the binding of BRD2, BRD3, and BRD4 to AcH4 with IC50 ranging from 92 to 112 nM, and inhibits the growth of a variety of human cancer cell lines with GI50 ranging from 60 to 200 nM. OTX015 results in rapid down-regulation of c-MYC expression, and show the synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines.
| [In vivo]
OTX015 (p.o.) significantly inhibits the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79% at 100 mg/kg qd and 61% at 10 mg/kg bid, respectively.
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| Hazard Information | Back Directory | [Uses]
(S)-2-(4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide is an orally bioavailable, inhibitor of BRD2, BRD3, and BRD4 to AcH4 and shows anti-tumor activity in vitro and in vivo tumor models. | [Definition]
ChEBI: 6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6s)- is an organonitrogen heterocyclic compound and an organosulfur heterocyclic compound. | [Biochem/physiol Actions]
It binds to bromodomain and extra-terminal domain (BET) proteins and inhibits their binding to the chromatin. This in turn prevents gene transcription. OTX015 has been shown to inhibit proliferation of cells in haematological malignancies. | [target]
BRD2 | [storage]
Store at -20°C |
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