OTX015 Chemical Properties

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

Safety Information

HS Code 

2934.99.3900

OTX015 Usage And Synthesis

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.

Description

The bromodomain and extra terminal domain (BET) family of proteins, including BRD2, BRD3, and BRD4, play a key role in many cellular processes, including inflammatory gene expression, mitosis, and viral/host interaction by controlling the assembly of histone acetylation-dependent chromatin complexes. OTX015 is an orally bioavailable, small molecule inhibitor of BRD2, BRD3, and BRD4 (EC₅₀s = 10-19 nM). It displays antiproliferative effects at a sub-micromolar range in vitro in a wide range of solid tumor types and leukemias, downregulating c-Myc expression and inducing cell cycle arrest and apoptosis. At 100 mg/kg, OTX015 has been shown to inhibit the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79%.

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

OTX015(202590-98-5)Related Product Information

• PFI-1
• I-BET151 (GSK1210151A)
• (+)-JQ1
• RVX-208
• CPI-203
• I-BET-762