Alvocidib HCl | Flavopiridol | CAS#146426-40-6 | CDK inhibitor

MedKoo Cat#: 200180 | Name: Alvocidib HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Alvocidib, also known as Flavoperidol, L868275 and HMR 1274, is a potent and selective CDK inhibitor with anti-inflammatory and anti-proliferative activities. Alvocidib may be useful in the treatment of various chronic diseases. Flavopiridol arrests cell cycle progression in the G1 or G2 phase by inhibiting the kinase activities of CDK1, CDK2, CDK4/6, and CDK7. Additionally, it binds tightly to CDK9, a component of the P-TEFb complex (CDK9/cyclin T), and interferes with RNA polymerase II activation and associated transcription. Flavopiridol elicits anti-inflammatory activity via CDK9 and NFκB-dependent signaling.

Chemical Structure

Alvocidib HCl

CAS#131740-09-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 200180

Name: Alvocidib HCl

CAS#: 131740-09-5 (HCl)

Chemical Formula: C21H21Cl2NO5

Exact Mass: 0.0000

Molecular Weight: 438.30

Elemental Analysis: C, 57.55; H, 4.83; Cl, 16.18; N, 3.20; O, 18.25

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,850.00	2 Weeks
1g	USD 4,250.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

131740-09-5 (HCl) 146426-40-6 (free base)

Synonym

Alvocidib; Alvocidib hydrochloride; Flavopiridol; HL 275; HL-275; HMR 1275; HMR-1275; L 86 8275; L86-8275; MDL 107,826A; MDL 107826A; MDL-107826A; NSC 649890.

IUPAC/Chemical Name

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

InChi Key

LGMSNQNWOCSPIK-LWHGMNCYSA-N

InChi Code

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

SMILES Code

O=C1C=C(C2=CC=CC=C2Cl)OC3=C1C(O)=CC(O)=C3[C@@H]4[C@H](O)CN(C)CC4.[H]Cl

Appearance

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

>5 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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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.

In vitro activity:

The proliferations of four CCA cell lines (KKU-055, KKU-100, KKU-213 and KKU-214) treated with flavopiridol (0, 50, 100, 200 and 300 nM) for 24, 48 and 72 h were analyzed by MTT assay. Flavopiridol potently inhibited proliferation in all CCA cell lines in a dose- and time-dependent manner (Fig. 1A). The half-maximal inhibitory concentrations (IC50) of flavopiridol at different time points were in the 40–213 nM range, as shown in Table 1. Reference: Heliyon. 2019 May; 5(5): e01675. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515137/

In vivo activity:

Alvocidib efficiently controlled tumor growth in a dose-dependent manner (Fig. 1). A dose of 5 mg/kg did not control tumor growth effectively, yet a dose of 10 mg/kg inhibited tumor growth. The SCID mice that received 10 mg/kg alvocidib showed a reduction in tumor growth by ∼50% compared with the control group. Reference: Surg Oncol. 2006 Aug;15(2):107-13. https://pubmed.ncbi.nlm.nih.gov/17097874/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.3	114.65
	DMF	22.5	51.36
	DMF:PBS (pH 7.2) (1:1)	0.5	1.14
	Ethanol	1.6	3.65
	Water	33.6	76.68

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 438.30 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Saisomboon S, Kariya R, Vaeteewoottacharn K, Wongkham S, Sawanyawisuth K, Okada S. Antitumor effects of flavopiridol, a cyclin-dependent kinase inhibitor, on human cholangiocarcinoma in vitro and in an in vivo xenograft model. Heliyon. 2019 May 9;5(5):e01675. doi: 10.1016/j.heliyon.2019.e01675. PMID: 31193061; PMCID: PMC6515137. 2. Zocchi L, Wu SC, Wu J, Hayama KL, Benavente CA. The cyclin-dependent kinase inhibitor flavopiridol (alvocidib) inhibits metastasis of human osteosarcoma cells. Oncotarget. 2018 May 4;9(34):23505-23518. doi: 10.18632/oncotarget.25239. PMID: 29805751; PMCID: PMC5955096. 3. Pinto N, Prokopec SD, Ghasemi F, Meens J, Ruicci KM, Khan IM, Mundi N, Patel K, Han MW, Yoo J, Fung K, MacNeil D, Mymryk JS, Datti A, Barrett JW, Boutros PC, Ailles L, Nichols AC. Flavopiridol causes cell cycle inhibition and demonstrates anti-cancer activity in anaplastic thyroid cancer models. PLoS One. 2020 Sep 24;15(9):e0239315. doi: 10.1371/journal.pone.0239315. PMID: 32970704; PMCID: PMC7514001. 4. Sato S, Kajiyama Y, Sugano M, Iwanuma Y, Sonoue H, Matsumoto T, Tsurumaru M. Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis. Surg Oncol. 2006 Aug;15(2):107-13. doi: 10.1016/j.suronc.2006.10.001. Epub 2006 Nov 13. PMID: 17097874.

In vitro protocol:

In vivo protocol:

1. Pinto N, Prokopec SD, Ghasemi F, Meens J, Ruicci KM, Khan IM, Mundi N, Patel K, Han MW, Yoo J, Fung K, MacNeil D, Mymryk JS, Datti A, Barrett JW, Boutros PC, Ailles L, Nichols AC. Flavopiridol causes cell cycle inhibition and demonstrates anti-cancer activity in anaplastic thyroid cancer models. PLoS One. 2020 Sep 24;15(9):e0239315. doi: 10.1371/journal.pone.0239315. PMID: 32970704; PMCID: PMC7514001. 2. Sato S, Kajiyama Y, Sugano M, Iwanuma Y, Sonoue H, Matsumoto T, Tsurumaru M. Alvocidib (Flavopiridol) suppresses tumor growth in SCID mice with human esophageal cancer xenografts without inducing apoptosis. Surg Oncol. 2006 Aug;15(2):107-13. doi: 10.1016/j.suronc.2006.10.001. Epub 2006 Nov 13. PMID: 17097874.

1: Pawde DM, Rahman SNR, Ponneganti S, Goswami A, Borkar RM, Shunmugaperumal T. Analytical Quality-by-Design-Based Systematic Optimization of RP-HPLC Method Conditions to Analyze Simultaneously Chloroquine Phosphate and Flavopiridol in Stress-Induced Combined Drug Solution and Pharmaceutical Emulsions. J Chromatogr Sci. 2022 Nov 10:bmac088. doi: 10.1093/chromsci/bmac088. Epub ahead of print. PMID: 36355561. 2: Gu L, Li C, Peng X, Lin H, Niu Y, Zheng H, Zhao G, Lin J. Flavopiridol Protects against Fungal Keratitis due to Aspergillus fumigatus by Alleviating Inflammation through the Promotion of Autophagy. ACS Infect Dis. 2022 Nov 11;8(11):2362-2373. doi: 10.1021/acsinfecdis.2c00427. Epub 2022 Oct 25. PMID: 36283079. 3: Sangsuwan R, Yik JHN, Owen M, Liu GY, Haudenschild DR, Lewis JS. Intra- articular injection of flavopiridol-loaded microparticles for treatment of post- traumatic osteoarthritis. Acta Biomater. 2022 Sep 1;149:347-358. doi: 10.1016/j.actbio.2022.06.042. Epub 2022 Jun 30. PMID: 35779774. 4: Jia Q, Hu Z, Song N, Mao W. Flavopiridol Mitigates the Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats by Targeting Cyclin- Dependent Kinase 9. Cardiovasc Drugs Ther. 2022 Jan 28. doi: 10.1007/s10557-021-07285-w. Epub ahead of print. PMID: 35088192. 5: Hassan MS, Cwidak N, Johnson C, Däster S, Eppenberger-Castori S, Awasthi N, Li J, Schwarz MA, von Holzen U. Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer. Front Pharmacol. 2021 Sep 21;12:746385. doi: 10.3389/fphar.2021.746385. PMID: 34621175; PMCID: PMC8490822. 6: Zhang XH, Hsiang J, Rosen ST. Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma. J Clin Haematol. 2021;2(2):48-61. doi: 10.33696/haematology.2.028. Epub 2021 May 4. PMID: 34223559; PMCID: PMC8248901. 7: Chen KTJ, Militao GGC, Anantha M, Witzigmann D, Leung AWY, Bally MB. Development and characterization of a novel flavopiridol formulation for treatment of acute myeloid leukemia. J Control Release. 2021 May 10;333:246-257. doi: 10.1016/j.jconrel.2021.03.042. Epub 2021 Mar 30. PMID: 33798663. 8: Pinto N, Prokopec SD, Ghasemi F, Meens J, Ruicci KM, Khan IM, Mundi N, Patel K, Han MW, Yoo J, Fung K, MacNeil D, Mymryk JS, Datti A, Barrett JW, Boutros PC, Ailles L, Nichols AC. Flavopiridol causes cell cycle inhibition and demonstrates anti-cancer activity in anaplastic thyroid cancer models. PLoS One. 2020 Sep 24;15(9):e0239315. doi: 10.1371/journal.pone.0239315. PMID: 32970704; PMCID: PMC7514001. 9: Ibrahim N, Bonnet P, Brion JD, Peyrat JF, Bignon J, Levaique H, Josselin B, Robert T, Colas P, Bach S, Messaoudi S, Alami M, Hamze A. Identification of a new series of flavopiridol-like structures as kinase inhibitors with high cytotoxic potency. Eur J Med Chem. 2020 Aug 1;199:112355. doi: 10.1016/j.ejmech.2020.112355. Epub 2020 May 5. PMID: 32402934. 10: Zhang C, Zhang Y, Qin Y, Zhang Q, Liu Q, Shang D, Lu H, Li X, Zhou C, Huang F, Jin N, Jiang C. Ifenprodil and Flavopiridol Identified by Genomewide RNA Interference Screening as Effective Drugs To Ameliorate Murine Acute Lung Injury after Influenza A H5N1 Virus Infection. mSystems. 2019 Dec 10;4(6):e00431-19. doi: 10.1128/mSystems.00431-19. PMID: 31822599; PMCID: PMC6906739. 11: Zalazar F, Luca P, Gardner K, Figg WD, Meiss R, Spallanzani RG, Vallecorsa P, Elguero B, Cotignola J, Vazquez E, Siervi A. Low Doses of CPS49 and Flavopiridol Combination as Potential Treatment for Advanced Prostate Cancer. Curr Pharm Biotechnol. 2019;20(12):1072. doi: 10.2174/138920102012190919103433. Erratum for: Curr Pharm Biotechnol. 2015;16(6):553-63. PMID: 31701844. 12: Miljkovic MD, Roschewski M, Dunleavy K, Wilson WH. Hybrid dosing of the cyclin-dependent kinase (CDK) inhibitor flavopiridol in relapsed/refractory mantle cell lymphoma and diffuse large B-cell lymphoma. Leuk Lymphoma. 2019 Dec;60(13):3320-3323. doi: 10.1080/10428194.2019.1627540. Epub 2019 Jun 17. PMID: 31204529; PMCID: PMC6917991. 13: Saisomboon S, Kariya R, Vaeteewoottacharn K, Wongkham S, Sawanyawisuth K, Okada S. Antitumor effects of flavopiridol, a cyclin-dependent kinase inhibitor, on human cholangiocarcinoma in vitro and in an in vivo xenograft model. Heliyon. 2019 May 9;5(5):e01675. doi: 10.1016/j.heliyon.2019.e01675. PMID: 31193061; PMCID: PMC6515137. 14: Re: Dasmahapatra G, Almenara JA, and Grant S, "Flavopiridol and Histone Deacetylase Inhibitors Promote Mitochondrial Injury and Cell Death in Human Leukemia Cells that Overexpress Bcl-2." Mol Pharmacol January 2006 69:288-298; doi:10.1124/mol.105.016154. Mol Pharmacol. 2019 Apr;95(4):335. doi: 10.1124/mol.105.016154retraction. PMID: 30824553; PMCID: PMC6402418. 15: Dogan Turacli I, Demirtas Korkmaz F, Candar T, Ekmekci A. Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells. J Cell Biochem. 2019 Apr;120(4):5628-5635. doi: 10.1002/jcb.27846. Epub 2018 Oct 14. PMID: 30317654. 16: Nilubol N, Boufraqech M, Zhang L, Gaskins K, Shen M, Zhang YQ, Gara SK, Austin CP, Kebebew E. Synergistic combination of flavopiridol and carfilzomib targets commonly dysregulated pathways in adrenocortical carcinoma and has biomarkers of response. Oncotarget. 2018 Aug 31;9(68):33030-33042. doi: 10.18632/oncotarget.26050. PMID: 30250647; PMCID: PMC6152480. 17: Zocchi L, Wu SC, Wu J, Hayama KL, Benavente CA. The cyclin-dependent kinase inhibitor flavopiridol (alvocidib) inhibits metastasis of human osteosarcoma cells. Oncotarget. 2018 May 4;9(34):23505-23518. doi: 10.18632/oncotarget.25239. PMID: 29805751; PMCID: PMC5955096. 18: Hu Z, Chen Y, Song L, Yik JHN, Haudenschild DR, Fan S. Flavopiridol Protects Bone Tissue by Attenuating RANKL Induced Osteoclast Formation. Front Pharmacol. 2018 May 3;9:174. doi: 10.3389/fphar.2018.00174. PMID: 29773986; PMCID: PMC5944179. 19: Rostam MA, Shajimoon A, Kamato D, Mitra P, Piva TJ, Getachew R, Cao Y, Zheng W, Osman N, Little PJ. Flavopiridol Inhibits TGF-β-Stimulated Biglycan Synthesis by Blocking Linker Region Phosphorylation and Nuclear Translocation of Smad2. J Pharmacol Exp Ther. 2018 Apr;365(1):156-164. doi: 10.1124/jpet.117.244483. Epub 2018 Feb 9. PMID: 29438988. 20: Erol A, Acikgoz E, Guven U, Duzagac F, Turkkani A, Colcimen N, Oktem G. Ribosome biogenesis mediates antitumor activity of flavopiridol in CD44+/CD24- breast cancer stem cells. Oncol Lett. 2017 Dec;14(6):6433-6440. doi: 10.3892/ol.2017.7029. Epub 2017 Sep 22. PMID: 29422957; PMCID: PMC5770605.