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Catalog No. | Product Name | Size | List Price (US$) | Quantity |
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The cheapest KB0742 (KB-0742, KB 0742) (CAS No.: 2416874-75-2) is for research use only. Significant discount for bulk order of KB0742. Condition of sample preparation and optimal sample dilution should be determined experimentally by the investigator.
Price/availability/specifications subject to change without notice. Unless otherwise indicated, our catalog and customized products are for research use only and not intended for human or animal diagnostic or therapeutic use.
Phone: 1-617-401-8149
Fax: 1-617-606-5019
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CAS No.: 2416874-75-2
IUPAC/Chemical Name: (R)-1-cyanobutan-2-yl ((S)-1-(3-(3-(3-methoxy-4-(oxazol-5-yl)phenyl)ureido)phenyl)ethyl)carbamate
Molecular Formula: C16H25N5•2HCl
Molecular Weight: 360.3
Purity: >99% pure by Achiral and Chiral HPLCs
QC: Achiral and Chiral HPLCs, MS, NMR, and Quantitative Elemental Analysis Report
Solubility: Soluble in Water (>18.6mg/ml, >50mM)
Storage: Store at 0 oC (short term), at -20 oC (long term), desiccated in a tightly
closed container. (Caution: Very Hygroscopic)
Note: Please contact us for COA, Spectra, and SDS information.
Background Information:
KB-0742 dihydrochloride (CAS No: 2416874-75-2) is a potent, selective and orally active CDK9 inhibitor with an IC550 of 6 nM for CDK9/cyclin T1. KB-0742 dihydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 dihydrochloride has potent anti-tumor activity.[1]
KB-0742 showed selectivity for CDK9 over other CDK family members, downregulated AR-dependent oncogenic transcription, and reduced tumor cell growth and promoted apoptosis in in vitro. Additionally, oral administration of KB-0742 (administered as a 3-day on/4-day off regimen) to mice that had been engrafted with castration resistant prostate cancer cells significantly inhibited tumor growth with modest effects on body weight. In a subsequent mouse xenograft study using a MYC-dependent acute myeloid leukemia model, KB-0742 administration again resulted in significant tumor growth inhibition with dose-dependent effects on pharmacodynamic markers of CDK9 inhibition in tumor. [2]
Target: CDK9/cyclinT1
IC50: 6 nM
In Vitro: KB-0742 (6 hours; 0.1-10 μM; 22Rv1 cells) treatment significant reduction of downstream phosphorylation of RNA Pol II at Ser2 and Ser7, and diminished phosphorylation at Ser5. Global androgen receptor (AR)-FL and AR-V protein levels are significantly reduced starting at 6 h treatment time, which is accompanied by the reduction of phospho-AR levels (Ser81).[1]
KB-0742 (48-72 hours) treatment shows cytostatic effects in prostate cancer and leukemia cell lines. KB-0742 shows antiproliferative activity with GR50s of 0.183 μM and 0.288 μM for 22Rv1 cells and MV-4-11 AML cells, respectively.[1]
In 22Rv1 cells, KB-0742 rapidly downregulates nascent transcription, preferentially depleting short half-life transcripts and AR-driven oncogenic programs.[1]
In Vivo: KB-0742 (3-30 mg/kg; p.o.; daily; over 21 days) is well tolerated even at high dose, while significantly reducing tumor burden in 22Rv1 human prostate cancer cell line-derived xenograft (CDX) models.[1]
What is the solubility of KB0742 in vitro?
H2O: 100 mg/mL (277.52 mM; Need ultrasonic); DMSO: 62.5 mg/mL (173.45 mM; Need ultrasonic)
What is the solubility of KB0742 in vivo?
1. Solvent: DMSO, PEG300, Tween-80, and saline
Please add 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline in order; solubility ≥ 2.08mg/mL.
2. DMSO and 20% SBE-β-CD in salin
Please add 10% DMSO and 90% (20% SBE-β-CD in saline) in order; solubility 2.08 mg/mL (need ultrasonic).
3. DMSO and corn oil
Please add 0% DMSO and 90% corn oil in order, solubility ≥ 2.08 mg/mL.
Reference:
[1]. Richters, A. et al. “Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors”, Cell Chem. Biol., 2021, 28, 134-147
[2]. Kronos Bio “A Dose Escalation and Cohort Expansion Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors or Non-Hodgkin Lymphoma”, ClinicalTrials.gov Identifier: NCT04718675.
[3]. Day, M. A. et al. “Abstract 1141: CDK9 inhibition is selective for transcriptionally addicted tumors harboring MYC genomic amplifications”, Cancer Res. 2021, DOI: 10.1158/1538-7445.AM2021-1141.
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