LY2835219 free base


Catalog No. size PriceQuantity
M6668-2 2mg solid $101
M6668-10 10mg solid $396

Description

Cas:1231929-97-7 (free base)

Product Information

LY2835219 free base is orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. LY2835219 inhibits CDK4 and CDK6 with low nanomolar potency. LY2835219 specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth.

 

Chemical Formula: C27H32F2N8

 

Exact Mass: 506.2718

 

Molecular Weight: 506.59339

 

Elemental Analysis: C, 64.01; H, 6.37; F, 7.50; N, 22.12

 

Synonym: 

 

LY2835219

LY 2835219

Abemaciclib

 

Chemical Name:  

N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine

 

InChi Key:

UZWDCWONPYILKI-UHFFFAOYSA-N

 

InChi Code:   InChI=1S/C27H32F2N8/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)

 

Smiles Code:

CC1=NC2=C(F)C=C(C3=NC(NC4=NC=C(CN5CCN(CC)CC5)C=C4)=NC=C3F)C=C2N1C(C)C

 

 

Technical Data:

 

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro

LY2835219 free base reduces cell viability with the IC50 values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells.

LY2835219 free base shows inhibition on A375R1-4, M14R, and SH4R with EC50 values ranging from 0.3 to 0.6 μM; Abemaciclib inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC50 values of 395, 260, and 463 nM, respectively.

LY2835219 free base inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells.

 

In Vivo

LY2835219 free base (45 mg/kg, p.o.) in combination with RAD001 causes a cooperative antitumor effect in HNSCC xenograft tumor.

LY2835219 free base (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model.

 

 

References

 

  1. Naz S, Sowers AL, Choudhuri R, Wissler MF, Gamson J, Mathias A, Cook JA, Mitchell JB. Abemaciclib, a Selective CDK4/6 Inhibitor Enhances the Radiosensitivity of Non-Small Cell Lung Cancer in vitro and in vivo. Clin Cancer Res. 2018 May 1. pii: clincanres.3575.2017. doi: 10.1158/1078-0432.CCR-17-3575. [Epub ahead of print] PubMed PMID: 29716919.

 

  1. Schaer DA, Beckmann RP, Dempsey JA, Huber L, Forest A, Amaladas N, Li Y, Wang YC, Rasmussen ER, Chin D, Capen A, Carpenito C, Staschke KA, Chung LA, Litchfield LM, Merzoug FF, Gong X, Iversen PW, Buchanan S, de Dios A, Novosiadly RD, Kalos M. The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade. Cell Rep. 2018 Mar 13;22(11):2978-2994. doi: 10.1016/j.celrep.2018.02.053. PubMed PMID: 29539425.

 

  1. Kotake T, Toi M. Abemaciclib for the treatment of breast cancer. Expert Opin Pharmacother. 2018 Apr;19(5):517-524. doi: 10.1080/14656566.2018.1448787. Epub 2018 Mar 9. PubMed PMID: 29522364.

 

  1. Corona SP, Generali D. Abemaciclib: a CDK4/6 inhibitor for the treatment of HR+/HER2- advanced breast cancer. Drug Des Devel Ther. 2018 Feb 16;12:321-330. doi: 10.2147/DDDT.S137783. eCollection 2018. Review. PubMed PMID: 29497278; PubMed Central PMCID: PMC5818877.

 

  1. O'Brien N, Conklin D, Beckmann R, Luo T, Chau K, Thomas J, Mc Nulty A, Marchal C, Kalous O, von Euw E, Hurvitz S, Mockbee C, Slamon DJ. Preclinical Activity of Abemaciclib Alone or in Combination with Antimitotic and Targeted Therapies in Breast Cancer. Mol Cancer Ther. 2018 May;17(5):897-907. doi: 10.1158/1535-7163.MCT-17-0290. Epub 2018 Feb 26. PubMed PMID: 29483214.

 

Products are for research use only. Not for human use.

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