Alvocidib
Identification
- Generic Name
- Alvocidib
- DrugBank Accession Number
- DB03496
- Background
Alvocidib is a synthetic flavonoid based on an extract from an Indian plant for the potential treatment of cancer. It works by inhibiting cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.
- Type
- Small Molecule
- Groups
- Experimental, Investigational
- Structure
Structure for Alvocidib (DB03496)
- Weight
- Average: 401.84
Monoisotopic: 401.103000462 - Chemical Formula
- C21H20ClNO5
- Synonyms
- Alvocidib
- Alvocidib freebase
- Flavopiridol
- External IDs
- L86-8275
Pharmacology
- Indication
Investigated for use/treatment in esophageal cancer, leukemia (lymphoid), lung cancer, liver cancer, and lymphoma (unspecified).
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
Inhibits cyclin-dependent kinases, arresting cell division and causing apoptosis in non-small lung cancer cells.
Target Actions Organism UCyclin-dependent kinase 2 inhibitorHumans UCyclin-dependent kinase 5 Not Available Humans UCyclin-dependent kinase 9 Not Available Humans UCyclin-dependent kinase 1 Not Available Humans UCyclin-dependent kinase 6 Not Available Humans UEpidermal growth factor receptor Not Available Humans UCyclin-dependent kinase 4 Not Available Humans UCyclin-dependent kinase 8 Not Available Humans UCyclin-dependent kinase 7 Not Available Humans UGlycogen phosphorylase, muscle form Not Available Humans UGlycogen phosphorylase, brain form Not Available Humans UGlycogen phosphorylase, liver form Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Abemaciclib may decrease the excretion rate of Alvocidib which could result in a higher serum level. Adenine The metabolism of Alvocidib can be decreased when combined with Adenine. Afatinib Afatinib may decrease the excretion rate of Alvocidib which could result in a higher serum level. Alectinib Alectinib may decrease the excretion rate of Alvocidib which could result in a higher serum level. Amitriptyline The metabolism of Alvocidib can be decreased when combined with Amitriptyline. Apalutamide Apalutamide may increase the excretion rate of Alvocidib which could result in a lower serum level and potentially a reduction in efficacy. Atazanavir The metabolism of Alvocidib can be decreased when combined with Atazanavir. Avanafil Avanafil may decrease the excretion rate of Alvocidib which could result in a higher serum level. Avatrombopag Avatrombopag may decrease the excretion rate of Alvocidib which could result in a higher serum level. Baricitinib Baricitinib may decrease the excretion rate of Alvocidib which could result in a higher serum level. 
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- Not Available
Products
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Ingredient UNII CAS InChI Key Alvocidib hydrochloride D48MS3A6N9 131740-09-5 LGMSNQNWOCSPIK-LWHGMNCYSA-N
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as flavones. These are flavonoids with a structure based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one).
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Flavonoids
- Sub Class
- Flavones
- Direct Parent
- Flavones
- Alternative Parents
- 5-hydroxyflavonoids / 7-hydroxyflavonoids / Phenylpiperidines / Chromones / 1-hydroxy-2-unsubstituted benzenoids / Pyranones and derivatives / Aralkylamines / Chlorobenzenes / Aryl chlorides / Heteroaromatic compounds show 10 more
- Substituents
- 1,2-aminoalcohol / 1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / 5-hydroxyflavonoid / 7-hydroxyflavonoid / Alcohol / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Aryl chloride show 30 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- monochlorobenzenes, hydroxypiperidine, dihydroxyflavone (CHEBI:47344)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 45AD6X575G
- CAS number
- 146426-40-6
- InChI Key
- BIIVYFLTOXDAOV-YVEFUNNKSA-N
- InChI
- InChI=1S/C21H20ClNO5/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/t12-,17+/m0/s1
- IUPAC Name
- 2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-4H-chromen-4-one
- SMILES
- CN1CC[C@@H]([C@H](O)C1)C1=C(O)C=C(O)C2=C1OC(=CC2=O)C1=CC=CC=C1Cl
References
- Synthesis Reference
Kyoung Soon Kim, "Process for the preparation of chiral ketone intermediates useful for the preparation of flavopiridol and analogs." U.S. Patent US5908934, issued March, 1998.
US5908934- General References
- Not Available
- External Links
- PDB Entries
- 1c8k / 1e1y / 3blr / 3ebp / 4o71
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.094 mg/mL ALOGPS logP 2.81 ALOGPS logP 2.48 ChemAxon logS -3.6 ALOGPS pKa (Strongest Acidic) 6.71 ChemAxon pKa (Strongest Basic) 7.36 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 90.23 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 107.74 m3·mol-1 ChemAxon Polarizability 40.85 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9932 Blood Brain Barrier - 0.557 Caco-2 permeable + 0.6029 P-glycoprotein substrate Substrate 0.9095 P-glycoprotein inhibitor I Non-inhibitor 0.8213 P-glycoprotein inhibitor II Non-inhibitor 0.7929 Renal organic cation transporter Non-inhibitor 0.6429 CYP450 2C9 substrate Non-substrate 0.7975 CYP450 2D6 substrate Non-substrate 0.6651 CYP450 3A4 substrate Substrate 0.6517 CYP450 1A2 substrate Non-inhibitor 0.6845 CYP450 2C9 inhibitor Non-inhibitor 0.8621 CYP450 2D6 inhibitor Non-inhibitor 0.7374 CYP450 2C19 inhibitor Non-inhibitor 0.7358 CYP450 3A4 inhibitor Non-inhibitor 0.9008 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8937 Ames test Non AMES toxic 0.7686 Carcinogenicity Non-carcinogens 0.9375 Biodegradation Not ready biodegradable 0.9923 Rat acute toxicity 2.7659 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5312 hERG inhibition (predictor II) Non-inhibitor 0.715
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, N...
- Gene Name
- CDK2
- Uniprot ID
- P24941
- Uniprot Name
- Cyclin-dependent kinase 2
- Molecular Weight
- 33929.215 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Tau-protein kinase activity
- Specific Function
- Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive...
- Gene Name
- CDK5
- Uniprot ID
- Q00535
- Uniprot Name
- Cyclin-dependent-like kinase 5
- Molecular Weight
- 33304.125 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcription regulatory region dna binding
- Specific Function
- Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), whic...
- Gene Name
- CDK9
- Uniprot ID
- P50750
- Uniprot Name
- Cyclin-dependent kinase 9
- Molecular Weight
- 42777.155 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Rna polymerase ii carboxy-terminal domain kinase activity
- Specific Function
- Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via...
- Gene Name
- CDK1
- Uniprot ID
- P06493
- Uniprot Name
- Cyclin-dependent kinase 1
- Molecular Weight
- 34095.14 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Cyclin-dependent protein serine/threonine kinase activity
- Specific Function
- Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during int...
- Gene Name
- CDK6
- Uniprot ID
- Q00534
- Uniprot Name
- Cyclin-dependent kinase 6
- Molecular Weight
- 36938.025 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Cyclin-dependent protein serine/threonine kinase regulator activity
- Specific Function
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S tra...
- Gene Name
- CDK4
- Uniprot ID
- P11802
- Uniprot Name
- Cyclin-dependent kinase 4
- Molecular Weight
- 33729.55 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Ubiquitin protein ligase activity
- Specific Function
- Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from ...
- Gene Name
- CDK8
- Uniprot ID
- P49336
- Uniprot Name
- Cyclin-dependent kinase 8
- Molecular Weight
- 53283.335 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Transcription coactivator activity
- Specific Function
- Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the ...
- Gene Name
- CDK7
- Uniprot ID
- P50613
- Uniprot Name
- Cyclin-dependent kinase 7
- Molecular Weight
- 39038.005 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Pyridoxal phosphate binding
- Specific Function
- Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known ...
- Gene Name
- PYGM
- Uniprot ID
- P11217
- Uniprot Name
- Glycogen phosphorylase, muscle form
- Molecular Weight
- 97091.265 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Pyridoxal phosphate binding
- Specific Function
- Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known ...
- Gene Name
- PYGB
- Uniprot ID
- P11216
- Uniprot Name
- Glycogen phosphorylase, brain form
- Molecular Weight
- 96695.18 Da
References
- Kaiser A, Nishi K, Gorin FA, Walsh DA, Bradbury EM, Schnier JB: The cyclin-dependent kinase (CDK) inhibitor flavopiridol inhibits glycogen phosphorylase. Arch Biochem Biophys. 2001 Feb 15;386(2):179-87. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Vitamin binding
- Specific Function
- Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known ...
- Gene Name
- PYGL
- Uniprot ID
- P06737
- Uniprot Name
- Glycogen phosphorylase, liver form
- Molecular Weight
- 97147.82 Da
References
- Kaiser A, Nishi K, Gorin FA, Walsh DA, Bradbury EM, Schnier JB: The cyclin-dependent kinase (CDK) inhibitor flavopiridol inhibits glycogen phosphorylase. Arch Biochem Biophys. 2001 Feb 15;386(2):179-87. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Nakanishi T, Karp JE, Tan M, Doyle LA, Peters T, Yang W, Wei D, Ross DD: Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res. 2003 Aug 15;9(9):3320-8. [Article]
- Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD: Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Mol Pharmacol. 2003 Dec;64(6):1452-62. [Article]
- Shi Z, Parmar S, Peng XX, Shen T, Robey RW, Bates SE, Fu LW, Shao Y, Chen YM, Zang F, Chen ZS: The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance. Oncol Rep. 2009 Feb;21(2):483-9. [Article]
Drug created on June 13, 2005 13:24 / Updated on August 07, 2021 00:40