1. Epigenetics
  2. Epigenetic Reader Domain

OTX-015 (Synonyms: MK-8628)

Cat. No.: HY-15743 Purity: 99.69%
Data Sheet SDS Handling Instructions

OTX-015 is a new potent BRD2/3/4 inhibitor for cell adhesion with IC50 values from 92 to 112 nM.

For research use only. We do not sell to patients.
OTX-015 Chemical Structure

OTX-015 Chemical Structure

CAS No. : 202590-98-5

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $420 In-stock
200 mg $800 In-stock
500 mg   Get quote  
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

OTX-015 is a new potent BRD2/3/4 inhibitor for cell adhesion with IC50 values from 92 to 112 nM.

IC50 & Target

IC50: 92-112 nM (BRD2, BRD3, BRD4)[1]

In Vitro

OTX015 (500 nM) exposure induces a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression is unchanged. c-MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels do correlate however with viability following exposure to OTX015. Sequential combinations of OTX015 with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line[2]. OTX015 (0.1, 1, 5 μM) treatment induces HIV-1 full-length transcripts and viral outgrowth in resting CD4+ T cells from infected individuals receiving suppressive antiretroviral therapy (ART), while exerting minimal toxicity and effects on T cell activation. OTX015-mediated activation of HIV-1 involves an increase in CDK9 occupancy and RNAP II C-terminal domain (CTD) phosphorylation[3].

In Vivo

In MDA-MB-231 murine xenografts, tumor mass is significantly (p < 0.05) reduced by OTX015 (50 mg/kg) with respect to vehicle-treated animals. OTX015 in combination with 2 mg/kg everolimus shows more effective activity than OTX015 alone[4].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02259114 Oncoethix GmbH NUT Midline Carcinoma|Triple Negative Breast Cancer|Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation|Castrate-resistant Prostate Cancer (CRPC)|Pancreatic Ductal Adenocarcinoma October 23, 2014 Phase 1
NCT02698176 Merck Sharp & Dohme Corp. NUT Midline Carcinoma (NMC)|Triple Negative Breast Cancer (TNBC)|Non-small Cell Lung Cancer (NSCLC)|Castration-resistant Prostate Cancer (CRPC) May 4, 2016 Phase 1
NCT01713582 Oncoethix GmbH Acute Myeloid Leukemia|Diffuse Large B-cell Lymphoma|Acute Lymphoblastic Leukemia|Multiple Myeloma December 2012 Phase 1
NCT02698189 Merck Sharp & Dohme Corp. AML Including AML de Novo and AML Secondary to MDS|DLBCL May 19, 2016 Phase 1
NCT02296476 Oncoethix GmbH Glioblastoma Multiforme October 2014 Phase 1|Phase 2
NCT02303782 Oncoethix GmbH Acute Myeloid Leukemia January 2015 Phase 1|Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.0326 mL 10.1628 mL 20.3256 mL
5 mM 0.4065 mL 2.0326 mL 4.0651 mL
10 mM 0.2033 mL 1.0163 mL 2.0326 mL
Kinase Assay
[3]

TZMbl cells, grown in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% FBS, are plated at 1×105 cells/well in 24-well culture plates 24 h before transfection and then transfected with Tat or pcDNA 3.1 plasmid using Lipofectamine 2000. Primary CD4+ T cells (5 × 106) isolated from healthy donors are transfected with Tat or pcDNA 3.1 plasmid at the presence of LTR-Luc construct and then plated in 6-well culture plates. At 24 h post-transfection, the cells are mock-treated or treated with OTX015. At 48 h post-treatment, cells are lysed and luciferase activity is measured using the Dual-Luciferase Reporter Assay Kit. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

OTX015 is dissolved in DMSO (1.0M stock solution).

For the MTT assay, cells are seeded in 24-well plates at 1×106 per well and treated with OTX015 (0.01 nM-10 μM) for 72 h. Cells are transferred to 96-well plates and incubated with 0.5 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in the dark at 37°C for 4 h. Cells are then lysed with 25% sodium dodecyl sulfate (SDS) lysis buffer and absorbance is read at 570 nm using a Microplate Reader. Three independent experiments are run for each cell line and untreated cells are used as negative controls.  MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[4]

OTX-015 is dissolved in water for oral administration.

Mice are subcutaneously injected in the right flank with 10×106 MDA-MB-231 cells. When average tumor weight is appr 130 mg, mice are randomized (nine animals/group) to one of the following experimental groups: vehicle (for OTX15, water, twice daily, oral; for everolimus vehicle, 5% Tween-80/5% polyethylene glycol 400, thrice weekly, intraperitoneal); 50 mg/kg OTX015, twice daily, oral; 2 mg/kg everolimus, thrice weekly, intraperitoneal; 50 mg/kg OTX015 + 2 mg/kg everolimus, according to the single agent dosing schedules. In the experiment with paclitaxel, mice are randomized (eight animals/group) to vehicle (cremophor:ethanol 1:1, then diluted 1:5 with saline; once weekly, intravenous) or 0.15 mg/kg paclitaxel, once weekly, intravenous. Mice are sacrified at the first sign of severe distress and tumors are collected. Tumor weight (1 mm3 = 1 mg) is determined using the formula d2 × D/2, where ‘d’ and ‘D’ are the minor and major diameters of the tumor in mm, respectively. Growth curves of each tumor are normalized with respect to volume at the start of treatment. The doubling time (Td) of each untreated tumor is calculated by exponential fit of the whole growth curve. Treatment efficacy is evaluated based on T/C%, absolute growth delay (AGD) and log cell kill (LCK) parameters. In T/C%, T and C are the mean tumor weight of treated and control groups, respectively. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

491.99

Formula

C₂₅H₂₂ClN₅O₂S

CAS No.

202590-98-5

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 49 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.69%

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Product Name:
OTX-015
Cat. No.:
HY-15743
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