Mocaciclib

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Mocaciclib

CAS 2766124-39-2

MF C33H36FN9O2 MW609.71

2-fluoro-N-[1-[2-[[[2-[[(3R,4R)-3-hydroxypiperidin-4-yl]methylamino]-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]phenyl]isoquinolin-6-yl]prop-2-enamide
2-Fluoro-N-[1-[2-[[[2-[[[(3R,4R)-3-hydroxy-4-piperidinyl]methyl]amino]-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazin-4-yl]amino]methyl]phenyl]-6-isoquinolinyl]-2-propenamide
2-fluoro-N-[1-[2-[[[2-[[(3R,4R)-3-hydroxypiperidin-4-yl]methylamino]-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-4-yl]amino]methyl]phenyl]isoquinolin-6-yl]prop-2-enamide

cyclin-dependent kinase (CDK) inhibitor, antineoplastic, Q 901, CDK7-IN-21,

OriginatorThe Lead Discovery Center; The Max Planck Institute of Biochemistry
DeveloperQurient Co
ClassAntineoplastics; Small molecules
Mechanism of ActionCyclin-dependent kinase-activating kinase inhibitors
Phase I/IISolid tumours
31 May 2024Preliminary efficacy, pharmacodynamics, pharmacokinetics and adverse events data from a phase I/II trial in Solid tumours presented at the 60th Annual Meeting of the American Society of Clinical Oncology (ASCO-2024)
21 May 2024Qurient Therapeutics enters into an Cooperative Research and Development Agreement (CRADA) with the US National Cancer Institute (NCI) for phase I/II trial in Small cell lung cancer (SCLC) and Solid tumours
21 May 2024Qurient Therapeutics plans phase I/II trial in Small cell lung cancer (SCLC) and Solid tumours

Mocaciclib (Q-901) is an orally bioavailable, selective cyclin-dependent kinase (CDK) inhibitor with potent activity against CDK2, CDK4, and CDK6. Preclinical data show that Mocaciclib inhibits CDK2/cyclin E with an IC₅₀ of 1.1 nM, CDK4/cyclin D1 with an IC₅₀ of 2.5 nM, and CDK6/cyclin D3 with an IC₅₀ of 4.1 nM, demonstrating high potency in enzymatic assays. In cancer cell lines, Mocaciclib suppresses retinoblastoma protein (Rb) phosphorylation, leading to G1 cell cycle arrest and growth inhibition in Rb-positive tumor models. It has shown antiproliferative effects in various preclinical models, including breast and lung cancers.

Mocaciclib is a selective inhibitor of cyclin-dependent kinase 7 (CDK7), with potential antineoplastic activity. Upon administration, mocaciclib selectively targets, covalently binds to and inhibits the activity of CDK7, thereby inhibiting CDK7-mediated signaling. The inhibition of CDK7 prevents phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II, thereby preventing transcription of important cancer-promoting genes. It prevents phosphorylation of the cell cycle kinases CDK1, 2, 4, and 6, thereby disrupting uncontrolled cell cycle progression. Altogether, this may induce apoptosis, cause cell cycle arrest, inhibit DNA damage repair and inhibit tumor cell proliferation in certain cancers that are dependent on CDK7-mediated transcriptional regulation and signaling. CDK7, a serine/threonine kinase, plays a role in controlling cell cycle progression and transcriptional regulation, and promotes the expression of key oncogenes through the phosphorylation of RNA polymerase II. It is overexpressed in multiple cancers.