Flavopiridol Hydrochloride

Flavopiridol Hydrochloride (Alvocidib Hydrochloride) is a broad inhibitor of CDK, competing with ATP to inhibit CDKs including CDK1, CDK2, CDK4 with IC50s of 30, 170, 100 nM, respectively.

Product information

CAS Number: 131740-09-5

Molecular Weight: 438.30

Formula: C21H21Cl2NO5

Synonym:

Alvocidib hydrochloride

Flavopiridol

HL 275

HL-275

HMR 1275

HMR-1275

L 86 8275

L86-8275

MDL 107826A

MDL-107826A

NSC 649890

MDL 107, 826A

Related CAS Number:

146426-40-6 (Alvocidib free base)

Chemical Name: 2-(2-chlorophenyl)-5, 7-dihydroxy-8-[(3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-chromen-4-one hydrochloride

Smiles: Cl.CN1C[C@@H](O)[C@H](CC1)C1=C2OC(=CC(=O)C2=C(O)C=C1O)C1=CC=CC=C1Cl

InChiKey: LGMSNQNWOCSPIK-LWHGMNCYSA-N

InChi: InChI=1S/C21H20ClNO5.ClH/c1-23-7-6-12(17(27)10-23)19-14(24)8-15(25)20-16(26)9-18(28-21(19)20)11-4-2-3-5-13(11)22;/h2-5,8-9,12,17,24-25,27H,6-7,10H2,1H3;1H/t12-,17+;/m0./s1

Technical Data

Appearance: Solid Power

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

Solubility: DMSO: 88 mg/mL(200.77 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Flavopiridol is initially found to inhibit the epidermal growth factor receptor and protein kinase A (IC50 = 21 and 122 μM). Flavopiridol is later shown to inhibit cell proliferation, at more physiologically relevant concentrations (IC50 = 66 nM) when Flavopiridol is tested in the National Cancer Institute Development Therapeutics Program panel of 60 human tumor cell lines. Flavopiridol induces G1 arrest with inhibition of CDK2 and CDK4 in human breast carcinoma cells in a time and concentration dependent manner. Short time treatment of Flavopiridol (~12 hours) induce apoptosis in hematopoietic cell lines including SUDHL4, SUDHL6 (B-cell lines), Jurkat and MOLT4 (T-cell lines ), and HL60 (myeloid). In the clonogenic assay, Flavopiridol functions as a highly potent cytotoxic compound with a mean IC70 with 8 ng/mL in 23 human tumor models. A recent study shows Flavopiridol treatment induces a substantial AKT-Ser473 phosphorylation in human glioblastoma T98G cell line.

In Vivo:

At the maximal tolerated dose of 10 mg/kg/day administered p.o. on days 1-4 and 7-11, Flavopiridol effects tumor regression in PRXF1337 and tumor stasis lasting for 4 weeks in PRXF1369. After treatment with 7.5 mg/kg Flavopiridol bolus intravenous (IV) or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts undergo complete regressions, and animals remain disease-free several months after one course of Flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days undergo either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay is 73.2%. Daily IV or IP administration of flavopiridol results in peak plasma levels of about 7 µM, followed by a progressive decline to approximately 100 nM in 8 hours.

References:

1. Parker BW, et al, Blood, 1998, 91(2), 458-465.
2. Carlson BA, et al, Cancer Res, 1996, 56(13), 2973-2978.
3. Senderowicz AM, Oncologist, 2002, 7 Suppl 3:12-9.

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