Sch 727965
[CAS# 779353-01-4]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Ethylpyridine
• Name: Sch 727965
• Synonyms: Dinaciclib; (2S)-1-[3-Ethyl-7-[[(1-oxido-3-pyridinyl)methyl]amino]pyrazolo[1,5-a]pyrimidin-5-yl]-2-piperidineethanol
• Molecular Formula: C₂₁H₂₈N₆O₂
• Molecular Weight: 396.49
• CAS Registry Number: 779353-01-4
• EC Number: 814-152-8
• SMILES: CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCC[C@H]4CCO

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Solubility: 79 mg/ml in DMSO (25°C) (Expl.)
• Index of refraction: 1.677 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H315-H319-H340-H372
• Safety Statements: P203-P260-P264-P264+P265-P270-P280-P302+P352-P305+P351+P338-P318-P319-P321-P332+P317-P337+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Germ cell mutagenicity	Muta.	1B	H340
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Sch 727965, also known as dinaciclib, is a synthetic small-molecule inhibitor primarily targeting cyclin-dependent kinases (CDKs). It was developed through medicinal chemistry efforts aimed at creating potent and selective inhibitors of CDKs involved in cell cycle regulation and transcription. The compound was discovered in the context of cancer drug development, as deregulation of CDKs is a common feature in various cancers.

Dinaciclib exhibits high affinity for CDK1, CDK2, CDK5, and CDK9, enzymes that play critical roles in cell cycle progression and transcriptional control. By inhibiting these kinases, Sch 727965 disrupts processes essential for tumor cell proliferation and survival, leading to cell cycle arrest and apoptosis in cancer cells.

This compound has been studied extensively in preclinical models and clinical trials for multiple types of cancer, including leukemia, lymphoma, and solid tumors such as breast and lung cancer. Its ability to target multiple CDKs simultaneously distinguishes it from earlier, less selective inhibitors, potentially enhancing its therapeutic efficacy.

Sch 727965 is administered intravenously in clinical settings, with dosing regimens designed to maximize tumor inhibition while managing toxicity. Common side effects observed during clinical trials include myelosuppression, fatigue, and gastrointestinal symptoms, consistent with its impact on rapidly dividing cells.

Beyond oncology, research has explored the potential of dinaciclib in other diseases where CDK dysregulation is implicated, although cancer remains the primary focus.

In summary, Sch 727965 is a cyclin-dependent kinase inhibitor developed to interfere with critical enzymes controlling cell division and transcription, making it a promising agent in cancer therapy. Its discovery has contributed to the broader understanding and therapeutic targeting of CDKs in oncology.

References

2011. The Cyclin-Dependent Kinase Inhibitor SCH 727965 (Dinacliclib) Induces the Apoptosis of Osteosarcoma Cells. Molecular Cancer Therapeutics, 10(6).
DOI: 10.1158/1535-7163.mct-11-0167

2011. Vinblastine sensitizes leukemia cells to cyclin-dependent kinase inhibitors, inducing acute cell cycle phase-independent apoptosis. Cancer Biology & Therapy, 12(4).
DOI: 10.4161/cbt.12.4.16909

2024. Anti-Tumor and Chemosensitizing Effects of the CDK Inhibitor Dinaciclib on Cholangiocarcinoma In Vitro and In Vivo. In Vivo, 38(5).
DOI: 10.21873/invivo.13693