ALK-IN-1

• CAT Number: I004989
• CAS Number: 1197958-12-5
• Molecular Formula: C26H34ClN6O2P
• Molecular Weight: 529.01
• Purity: ≥95%
• Synonyms: (2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide
• Target: Anaplastic lymphoma kinase (ALK)
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4°C for short term ,or -20 °C for long term
• InChI: InChI=1S/C26H34ClN6O2P/c1-32(2)18-12-14-33(15-13-18)19-10-11-21(23(16-19)35-3)30-26-28-17-20(27)25(31-26)29-22-8-6-7-9-24(22)36(4,5)34/h6-11,16-18H,12-15H2,1-5H3,(H2,28,29,30,31)
• InChIKey: OVDSPTSBIQCAIN-UHFFFAOYSA-N
• SMILES: CP(C)(C1=CC=CC=C1NC2=NC(NC3=CC=C(N4CCC(N(C)C)CC4)C=C3OC)=NC=C2Cl)=O

ALK-IN-1 (CAT: I004989) is a small molecule inhibitor that targets anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in cell growth and proliferation. It exhibits potent inhibitory activity against ALK, blocking its signaling pathway and inhibiting tumor cell growth. ALK-IN-1 has shown promising results in preclinical studies, demonstrating efficacy in inhibiting ALK-positive cancer cells, including non-small cell lung cancer (NSCLC) and neuroblastoma. It holds potential as a targeted therapy for ALK-driven cancers and may contribute to the development of novel treatment strategies for these malignancies.

Reference

1. J Med Chem. 2016 May 26;59(10):4948-64. doi: 10.1021/acs.jmedchem.6b00306. Epub
2016 May 12.
Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally
Active Inhibitor of Anaplastic Lymphoma Kinase.
Huang WS(1), Liu S(1), Zou D(1), Thomas M(1), Wang Y(1), Zhou T(1), Romero J(1),
Kohlmann A(1), Li F(1), Qi J(1), Cai L(1), Dwight TA(1), Xu Y(1), Xu R(1), Dodd
R(1), Toms A(1), Parillon L(1), Lu X(1), Anjum R(1), Zhang S(1), Wang F(1), Keats
J(1), Wardwell SD(1), Ning Y(1), Xu Q(1), Moran LE(1), Mohemmad QK(1), Jang
HG(1), Clackson T(1), Narasimhan NI(1), Rivera VM(1), Zhu X(1), Dalgarno D(1),
Shakespeare WC(1).
Author information:
(1)ARIAD Pharmaceuticals, Inc. , 26 Landsdowne Street, Cambridge, Massachusetts
02139, United States.
In the treatment of echinoderm microtubule-associated protein-like 4
(EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer
(NSCLC), secondary mutations within the ALK kinase domain have emerged as a major
resistance mechanism to both first- and second-generation ALK inhibitors. This
report describes the design and synthesis of a series of
2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating
in identification of the investigational clinical candidate brigatinib. A unique
structural feature of brigatinib is a phosphine oxide, an overlooked but novel
hydrogen-bond acceptor that drives potency and selectivity in addition to
favorable ADME properties. Brigatinib displayed low nanomolar IC50s against
native ALK and all tested clinically relevant ALK mutants in both enzyme-based
biochemical and cell-based viability assays and demonstrated efficacy in multiple
ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas
[ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced
phosphine oxide-containing drug candidate to date and is currently being
evaluated in a global phase 2 registration trial.