Fadraciclib

SKU: orb1296241

Description

Fadraciclib (CYC065) is a potent, orally bioavailable inhibitor targeting CDK2 and CDK9 kinases with IC50 values of 5 nM and 26 nM, respectively. It is used in cancer research to study transcriptional regulation and apoptosis, demonstrating activity in both in vitro cell-based assays and in vivo tumor models.

Research Area

Cell Biology

Key Properties

• CAS Number: 1070790-89-4
• MW: 397.52
• Purity: 99.75% (May vary between batches)
• Formula: C₂₁H₃₁N₇O
• SMILES: CC[C@H](Nc1nc(NCc2cnc(C)cc2C)c2ncn(C(C)C)c2n1)[C@@H](C)O
• Target: CDK
• Solubility: DMSO:100 mg/mL (251.56 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (10.06 mM)

Bioactivity

• Target IC50:
  CDK2:5 nM|CDK9:26 nM
• In Vivo:
  USC-ARK-2-derived xenografts are treated daily with CYC065 (22.5 mg/kg) for a 3-week period. Tumor size and mouse weight are recorded two times a week. The daily administration of CYC065 results in a significant reduction of tumor growth compared with the vehicle-treated mice (P=0.012 starting at day 9 of the treatment). No significant weight loss is reported during the entire treatment period .
• In Vitro:
  CYC065 blocks cells in the G1 phase of the cell cycle and inhibits cell growth specifically in cyclin E1 (CCNE1)-overexpressing uterine serous carcinomas (USCs). USC cell lines expressing high CCNE1 mRNA and protein levels to be significantly more sensitive to treatment with CYC065 in vitro when compared with low CCNE1-expressing cell lines (IC50: mean±s.d.=124.1±57.8 nM in CCNE1-overexpressing USC cell lines vs 415±117.5 nM in CCNE1 low expressors, respectively; P=0.0003). Importantly, low concentrations of CYC065 (i.e., 100 nM) causes an arrest in the G1 phase of the cell cycle only in the CCNE1-overexpressing USC cell lines .
• Cell Research:
  Briefly, tumour cells are plated in six-well plates and treated with a titration of CYC065 concentrations (i.e., ranging from 100 to 500 nM). After 72 h, cells are harvested, washed and stained with propidium iodide (PI; 5 μg/mL) for flow cytometric counts. The percentage of viable cells is then normalized considering the vehicle-treated cells as 100% viable. Half-maximal inhibitory concentration values are determined using GraphPad Prism5 version 6. For drug combination studies, USC-ARK-1 and USC-ARK-2 cell lines are incubated with the combination of Taselisib and CYC065 at multiple paired concentrations including the IC50, the IC50/2 and the IC50*2 of each cell line to the corresponding drug (i.e., 10 nM of Taselisib and 198 nM of CYC065 for USC-ARK-1 and 50 nM of Taselisib and 62.5 nM of CYC065 for USC-ARK-2). Synergism is assessed by the combination index (CI). CI values <1 define a synergistic activity of the combination treatment. The CI values are calculated using the CompuSyn software .
• Animal Research:
  Briefly, 5-7-week-old SCID mice are injected into the subcutaneous region with USC cells. A minimum of five animals per group are used. Treatments are administrated by oral gavage starting 1 week after tumor implantation when the size of the tumor is 0.125-0.150 cm3. Uterine serous carcinoma-ARK-2-derived xenografts are divided into two groups: one group of animal receive the vehicle, whereas the experimental group receives CYC065 (22.5 mg/kg daily for 3 weeks). Uterine serous carcinoma-ARK-1-derived xenografts are instead divided into four groups: one group receive the vehicle (0.5% methylcellulose-0.2% Tween-80), one group receive CYC065 (22.5 mg/kg daily for 3 weeks), one group receive Taselisib (10 mg/kg daily, 5 days per week per 3 weeks) and the last group receive the combination of CYC065 and Taselisib. The size of the tumor at the initiation of treatment is 0.125-0.150 cm3. Mouse weight and tumor size is recorded two times a week for the entire experimental period. Tumor volume is calculated.

Storage & Handling

• Storage: Pure form: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CDK9, CDK, CDK2, Cyclin dependent kinase, CYC 065, CYC065, CYC-065, inhibit, Fadraciclib, Inhibitor

Compound Identifiers

PubChem CID

24983461