OKI-005
OKI-005 is an orally active inhibitor of Class I HDACs, with primary targeting of HDAC1, HDAC2 and HDAC3. OKI-005 is a prodrug of OKI-006 (HY-144893). OKI-005 increases histone acetylation levels, induces apoptosis and inhibits cancer cell proliferation. OKI-005 can be used in research related to triple-negative breast cancer and colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 1351479-95-2
- Formula: C29H44N4O6S2
- Molecular Weight:608.81
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
OKI-005 (0-5 μM; 72 h) potently inhibits the proliferation of most human triple-negative breast cancer (TNBC) and colorectal cancer (CRC) cell lines in vitro, with IC50 values of < 500 nM for most cell lines and IC50 values of < 100 nM for the most sensitive cell lines[1].
OKI-005 (0-500 nM; 24-48 h) induces concentration-dependent apoptosis (measured via caspase-3/7 activity) in sensitive human triple-negative breast cancer (TNBC) cell lines CAL-120 and MDA-MB-231, with activity increased by up to 9-fold, while exerting minimal effects on drug-resistant cell lines HCC1395 and Hs578T[1].
OKI-005 (0-200 nM; 24 h) alters the cell cycle distribution of human triple-negative breast cancer (TNBC) cell lines CAL-120 and MDA-MB-231, increasing the proportion of G1-phase cells and decreasing the proportion of S-phase cells after 24 h of incubation[1].
OKI-005 (0-500 nM; 24 h) induces concentration-dependent increases in acetylated histone H3 and p21 (class I HDAC inhibition markers) in both sensitive and drug-resistant human triple-negative breast cancer (TNBC) cell lines, with only a slight increase in acetylated α-tubulin observed at the highest tested concentration (500 nM)[1].
Combination treatment with OKI-005 (0.1-0.4 μM; 72 h) and Doxorubicin (HY-15142A) exerts synergistic antiproliferative activity in the triple-negative breast cancer (TNBC) cell lines CAL-51, MDA-MB-231, Hs 578T and CAL-120, and this effect is independent of p53 status[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human TNBC cell lines CAL-120, MDA-MB-231, HCC1395, Hs578T
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Concentration:0, 7.8, 15.6, 31.3, 62.5, 125, 250 and 500 nM
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Incubation Time:24 h; 48 h
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Result:Induced a concentration-dependent increase in caspase-3/7 activity in sensitive TNBC cell lines CAL-120 and MDA-MB-231, with up to a 7-9-fold increase compared to untreated controls.
Caused minimal increase in apoptosis in resistant TNBC cell lines HCC1395 and Hs578T.
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Cell Line:Human TNBC cell lines CAL-120 and MDA-MB-231
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Concentration:0, 25, 100 and 200 nM
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Incubation Time:24 h
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Result:Resulted in a trend toward an increase in the G1 cell fraction and a decrease in the S phase cell fraction in CAL-120 cells.
Caused a statistically significant shift to G1 and reduction in S phase in MDA-MB-231 cells.
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Cell Line:Human TNBC cell lines (sensitive and resistant lines, including CAL-120, MDA-MB-231, HCC1395, Hs578T)
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Concentration:0 nM, 50 nM, 200 nM, 500 nM
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Incubation Time:24 h
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Result:Induced a concentration-dependent increase in acetylated histone H3 and p21 expression in both sensitive and resistant TNBC cell lines, consistent with class I HDAC inhibition.
Caused a small increase in acetylated α-tubulin at the highest dose (500 nM), potentially indicating weak class IIb HDAC inhibition.
OKI-005 (10 mg/kg; i.p.; three times per week; 30 days) statistically significantly inhibits primary triple-negative breast tumor growth and metastasis in BALB/c mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 6-8 weeks old)[1]
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Dosage:5 mg/kg; 10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 14 days; i.p.; daily; 14 days
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Result:Achieved statistically significant tumor growth inhibition of 28.1% at 30 mg/kg p.o. compared to vehicle control.
Achieved statistically significant tumor growth inhibition of 75.6% at 100 mg/kg p.o. compared to vehicle control.
Induced dose-dependent increase in acetyl-histone H3 and acetyl H3K9 at 1 hour post-dose.
Exerted time-dependent increase in acetyl-histone H3 and acetyl H3K9 at 100 mg/kg p.o., with highest levels at 4 hours post-treatment and return to baseline by 24 hours.
Caused weight loss requiring dose reduction in mice treated with 100 mg/kg p.o. at ~1 week.
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Animal Model:BALB/c[1]
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Dosage:10 mg/kg
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Administration:i.p.; three times per week; 30 days
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Result:Statistically significantly inhibited primary tumor growth compared to vehicle control.
Reduced the number of observed thoracic metastases compared to vehicle control.
Chemical Information
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CAS No. 1351479-95-2
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Molecular Weight 608.81
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Formula C29H44N4O6S2
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SMILES
O=C1C2=CSC(CNC(C[C@H](OC([C@@H](NC(C(C)(N1)C)=O)C(C)C)=O)/C=C/CCSC(CCCCCCC)=O)=O)=N2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Diamond JR, et al. Preclinical Development of the Class-I-Selective Histone Deacetylase Inhibitor OKI-179 for the Treatment of Solid Tumors. Mol Cancer Ther. 2022;21(3):397-406. [Content Brief]
[2]. Smoots SG, et al. Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis. Breast Cancer Res. 2024;26(1):35. Published 2024 Mar 1. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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