ALVOCIDIB

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H20ClNO5
Molecular Weight	401.84
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CC[C@@H]([C@H](O)C1)C2=C(O)C=C(O)C3=C2OC(=CC3=O)C4=CC=CC=C4Cl

InChI

InChIKey=BIIVYFLTOXDAOV-YVEFUNNKSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H20ClNO5
Molecular Weight	401.84
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27118540
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00020332 | https://clinicaltrials.gov/ct2/show/NCT00020189 | https://clinicaltrials.gov/ct2/show/NCT00464633 | https://clinicaltrials.gov/ct2/show/NCT00445341

Alvocidib (also known as Flavopiridol or HMR-1275) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development for the treatment of acute myeloid leukemia, by Tolero Pharmaceuticals, Inc. As a broad spectrum CDK inhibitor, Alvocidib can inhibit cell cycle progression in either G1 or G2 and induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. Alvocidib exhibits potent cytotoxicity against a wide variety of tumor cell lines (LNCAP, HCT116, A2780, K562, PC3, and Mia PaCa-2) with IC50 values ranging from 16 nM for LNCAP to 130 nM for K562. Administration of Alvocidib at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, and active against the human A2780 ovarian carcinoma implanted sc in nude mice). Alvocidib treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. Tolero Pharmaceuticals Inc. announced that the FDA has granted orphan drug designation for Alvocidib, its cyclin-dependent kinase small molecule inhibitor, for the treatment of patients with acute myeloid leukemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclin-dependent kinase 4 26 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	3.3 nM [Kd]
Cyclin-dependent kinase 9 24 Target ID: CHEMBL3116 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23252711	Inhibitor 8504	3.0 nM [Ki]
Cyclin-dependent kinase-like 5 3 Target ID: CHEMBL1163112 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	7.1 nM [Kd]
Serine/threonine-protein kinase ICK 3 Target ID: CHEMBL1163126 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	0.69 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Head and neck cancer 50 Sources: https://clinicaltrials.gov/ct2/show/NCT00020189	Primary	Phase II 1147	Unknown Approved Use Unknown
Thromboembolism 8 Sources: https://clinicaltrials.gov/ct2/show/NCT00020189	Primary	Phase II 1147	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://clinicaltrials.gov/ct2/show/NCT00020332	Primary	Phase II 1147	Unknown Approved Use Unknown
Adult acute megakaryoblastic leukemia 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00634244	Primary	Phase II 1147	Unknown Approved Use Unknown
Chronic lymphocytic leukemia 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00464633	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.78 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20460644	100 mg 1 times / day steady-state, intravenous dose: 100 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ALVOCIDIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
11.2 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20460644	100 mg 1 times / day steady-state, intravenous dose: 100 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ALVOCIDIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.84 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/20460644	100 mg 1 times / day steady-state, intravenous dose: 100 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		ALVOCIDIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP1 116	OATP2B1 122 UGT1A3 470 UGT2B4 278 UGT2B28 65 UGT1A4 399 P-gp 2052 UGT2B7 456 UGT1A7 249 OATP1B1 503 UGT2B10 131 UGT1A1 479 UGT1A8 323 BCRP 697 UGT1A9 423 MRP1 113 UGT2B11 4 UGT1A10 331 OATP1B3 435 UGT2B15 236 UGT1A5 56 UGT1A6 343 UGT2B17 237

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10496352/	yes

Drug as victim

Target	Modality	Activity
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	major [Km 37 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	minor
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12960118/ \| https://pubmed.ncbi.nlm.nih.gov/11205902/	no
UGT1A5 56	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B10 131	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B11 4	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B28 65	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12069159/	no
OATP2B1 122	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25351763/	yes [Km 175 uM]
OATP1B1 503	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25351763/	yes [Km 66 uM]
OATP1B3 435	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25351763/	yes [Km 66.8 uM]
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11205902/	yes
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11205902/ \| https://pubmed.ncbi.nlm.nih.gov/10496352/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116199	https://www.001chemical.com/chem/search?q=DY116199
1PlusChem LLC	1P001EGY	https://www.1pchem.com/search?query=1P001EGY
1PlusChem LLC	1P0038M1	https://www.1pchem.com/search?query=1P0038M1
AChemBlock	P50930	http://www.achemblock.com/catalogsearch/result/?q=P50930
AK Scientific	2106AH	https://aksci.com/item_detail.php?cat=2106AH
Ambeed	A180731	http://www.ambeed.com/search/Search.html?keyword=A180731
Apollo Scientific	BIA8419	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIA8419&product_group=%25&search_fieldname=header_search
AstaTech	44223	http://astatechinc.com/CPSResult.php?CRNO=44223
AstaTech	C72284	http://astatechinc.com/CPSResult.php?CRNO=C72284
BioSynth	J-500011	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-500011
BLD Pharm	BD130402	http://www.bldpharm.com/search/Search.html?keyword=BD130402
BLD Pharm	BD130403	http://www.bldpharm.com/search/Search.html?keyword=BD130403
Capot Chemical	22427	https://www.capotchem.com/search.do?q=22427
Cayman Chemical	10009197	http://www.caymanchem.com/app/template/Product.vm/catalog/10009197
Chem Scene	CS-0018	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0018
Chem Scene	CS-0306	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0306
ChemShuttle	111849	https://www.chemshuttle.com/catalogsearch/result/?q=111849
ChemShuttle	112400	https://www.chemshuttle.com/catalogsearch/result/?q=112400
eMolecules	195179259	https://orderbb.emolecules.com/search/#?query=195179259
eMolecules	195315725	https://orderbb.emolecules.com/search/#?query=195315725
eMolecules	300450414	https://orderbb.emolecules.com/search/#?query=300450414
eMolecules	32176532	https://orderbb.emolecules.com/search/#?query=32176532
eMolecules	37153211	https://orderbb.emolecules.com/search/#?query=37153211
eNovation Chemicals	D372517	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372517&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D395215	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395215&searchbtn.x=0&searchbtn.y=0
Hairui	HR110880	http://www.hairuichem.com/en/product/search.do?q=HR110880
Hairui	HR134920	http://www.hairuichem.com/en/product/search.do?q=HR134920
KeyOrganics	AS-58704	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-58704
KeyOrganics	AS-74761	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74761
Matrix Scientific	132605	http://www.matrixscientific.com/132605.html
Matrix Scientific	147197	http://www.matrixscientific.com/147197.html
mcule	MCULE-2051857153	https://mcule.com/MCULE-2051857153/
mcule	MCULE-2249432897	https://mcule.com/MCULE-2249432897/
mcule	MCULE-7025192771	https://mcule.com/MCULE-7025192771/
mcule	MCULE-9910962066	https://mcule.com/MCULE-9910962066/
MedChem Express	HY-10005	https://www.medchemexpress.com/search.html?q=HY-10005&ft=&fa=&fp=
MedChem Express	HY-10006	https://www.medchemexpress.com/search.html?q=HY-10006&ft=&fa=&fp=
Molcore	MC116199	http://www.molcore.com/CatMC116199.html
Molnova	M11289	https://www.molnova.com/en/serch-list.html?keywords=M11289
Molnova	M11992	https://www.molnova.com/en/serch-list.html?keywords=M11992
MolPort	MolPort-006-169-102	https://www.molport.com/shop/molecule-link/MolPort-006-169-102
MolPort	MolPort-006-394-122	https://www.molport.com/shop/molecule-link/MolPort-006-394-122
MolPort	MolPort-039-139-196	https://www.molport.com/shop/molecule-link/MolPort-039-139-196
MuseChem	I001773	https://www.musechem.com/product/I001773.html
MuseChem	I001813	https://www.musechem.com/product/I001813.html
Selleck Chemicals	S2679	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2679
ShangHai Biochempartner	BCP000467	http://www.biochempartner.com/search_BCP000467
TargetMol	T2615	https://www.targetmol.com/search?keyword=T2615
TargetMol	T6837	https://www.targetmol.com/search?keyword=T6837
Tocris	3094	https://www.tocris.com/search.php?Type=QuickSearch&Value=3094
Toronto Research Chemicals	C181227	https://www.trc-canada.com/product-detail/?CatNum=C181227
Toronto Research Chemicals	F373000	https://www.trc-canada.com/product-detail/?CatNum=F373000
W&J PharmaChem	RT-	http://wjpharmachem.com/new/searcht.php?keyword=RT-

PubMed

Title	Date	PubMed
Conversion of drug-induced differentiation to apoptosis by pharmacologic cyclin-dependent kinase inhibitors.	2003-01-28	12548009
Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis.	2003-01-01	12517802
Flavopiridol down-regulates antiapoptotic proteins and sensitizes human breast cancer cells to epothilone B-induced apoptosis.	2003-01-01	12517783
Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial.	2003-01	12538483
Protein kinase C-dependent activation of the tumor necrosis factor receptor-mediated extrinsic cell death pathway underlies enhanced apoptosis in human myeloid leukemia cells exposed to bryostatin 1 and flavopiridol.	2003-01	12533676
Flavopiridol-induced apoptosis is mediated through up-regulation of E2F1 and repression of Mcl-1.	2003-01	12533675
Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells.	2003-01	12457721
Signal transduction--directed cancer treatments.	2003	12195027
Activation of the Rb/E2F1 pathway by the nonproliferative p38 MAPK during Fas (APO1/CD95)-mediated neuronal apoptosis.	2002-12-13	12351630
Cyclin-dependent kinases as cellular targets for antiviral drugs.	2002-12	12460995
Pharmacological treatments for prostate cancer.	2002-12	12457434
Phase I clinical and pharmacokinetic trial of the cyclin-dependent kinase inhibitor flavopiridol.	2002-12	12451473
New insights in the transcriptional activity and coregulator molecules in the arterial wall.	2002-12	12419552
Role reversal for anticancer agents.	2002-11-15	12432260
Flavopiridol inversely affects p21(WAF1/CIP1) and p53 and protects p21-sensitive cells from paclitaxel.	2002-11-15	12432259
CDK inhibitors: cell cycle arrest versus apoptosis.	2002-11-14	12429920
The cyclin-dependent kinase inhibitor flavopiridol induces apoptosis in multiple myeloma cells through transcriptional repression and down-regulation of Mcl-1.	2002-11	12429644
New anti-HIV agents and targets.	2002-11	12369088
Phase I clinical and pharmacokinetic study of flavopiridol administered as a daily 1-hour infusion in patients with advanced neoplasms.	2002-10-01	12351605
Cyclin-dependent kinases as new targets for the prevention and treatment of cancer.	2002-10	12512390
HIV-1 expression induces cyclin D1 expression and pRb phosphorylation in infected podocytes: cell-cycle mechanisms contributing to the proliferative phenotype in HIV-associated nephropathy.	2002-09-19	12241561
[Report on 93rd AACR].	2002-09-06	12206987
Clinical trials referral resource. Flavopiridol.	2002-09	12380947
Flavopiridol potentiates STI571-induced mitochondrial damage and apoptosis in BCR-ABL-positive human leukemia cells.	2002-09	12231544
A high-performance liquid chromatography method using ultraviolet detection for the quantitation of flavopiridol from human plasma.	2002-09	12228893
ErbB2 overexpression in an ovarian cancer cell line confers sensitivity to the HSP90 inhibitor geldanamycin.	2002-08-15	12174876
Loss of the Bcl-2 phosphorylation loop domain is required to protect human myeloid leukemia cells from flavopiridol-mediated mitochondrial damage and apoptosis.	2002-08-13	12170773
Hematologic malignancies: new developments and future treatments.	2002-08	12170431
Progress toward the development of agents to modulate the cell cycle.	2002-08	12133723
New developments in anti-HIV chemotherapy.	2002-07-18	12084468
Drg1, a novel target for modulating sensitivity to CPT-11 in colon cancer cells.	2002-07-15	12124325
Targeting the cell cycle for cancer therapy.	2002-07-15	12107831
Flavopiridol and trastuzumab synergistically inhibit proliferation of breast cancer cells: association with selective cooperative inhibition of cyclin D1-dependent kinase and Akt signaling pathways.	2002-07	12479366
Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA).	2002-07	12094258
Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma.	2002-06-10	12115498
Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals.	2002-06-10	12069692
Review of flavopiridol, a cyclin-dependent kinase inhibitor, as breast cancer therapy.	2002-06	12138401
Synergistic induction of apoptosis in human myeloid leukemia cells by phorbol 12-myristate 13-acetate and flavopiridol proceeds via activation of both the intrinsic and tumor necrosis factor-mediated extrinsic cell death pathways.	2002-06	12021392
In vitro characterization of hepatic flavopiridol metabolism using human liver microsomes and recombinant UGT enzymes.	2002-05	12069159
Evidence for CRK3 participation in the cell division cycle of Trypanosoma cruzi.	2002-05	12034456
Flavopiridol, a novel cyclin-dependent kinase inhibitor, in clinical development.	2002-05	11978170
Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated excitotoxicity.	2002-05	11961048
Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.	2002-04-26	12054639
Highlights in the development of new antiviral agents.	2002-04	12370077
Seventy-two hour continuous infusion flavopiridol in relapsed and refractory mantle cell lymphoma.	2002-04	12153166
The cyclin-dependent kinase inhibitor flavopiridol disrupts sodium butyrate-induced p21WAF1/CIP1 expression and maturation while reciprocally potentiating apoptosis in human leukemia cells.	2002-02	12467221
Cytotoxic agents in the era of molecular targets and genomics.	2002	12165653
The cell cycle as a target for cancer therapy: basic and clinical findings with the small molecule inhibitors flavopiridol and UCN-01.	2002	12165651
Finding the needle in the haystack: why high-throughput screening is good for your health.	2002	12100740
Perspectives for cancer therapies with cdk2 inhibitors.	2001-12	12030783

Patents

Sample Use Guides

In Vivo Use Guide

30 mg/m2 as a 30-minute intravenous (IV) infusion followed by 30 mg/m2 as a 4-hour continuous infusion. Cycles with 4-week treatment with alvocidib followed by 2-week rest period for up to a maximum of 6 cycles

Route of Administration: Intravenous

In Vitro Use Guide

Skov-3 and BG-1 human ovarian cancer cells were used for activity evaluation. Cells (104/ml) were distributed into 96 well plates (“Greiner”, Frickenhausen, Germany) and allowed to adhere for 24 h. Medium was replaced by fresh medium containing vehicle or treatment reagents (Alvocidib 0.01, 0.1, 1, 10 ,100, 100 nM). After the indicated treatment period, cells were fixed by adding 10% glutamatealdehyde (“Merck”, Darmstadt, Germany) solution and stained by 0.05% crystal violet (“Sigma”) in 25% methanol. Following washing three times with double distilled water, cell bound crystal violet was dissolved in 0.1 M sodium citrate and measured at 560 nm (“ELISA Reader, Tecan”, Grödig, Austria). Experiments repeated in triplicate.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 06:54:14 GMT 2025` Edited by `admin` on `Wed Apr 02 06:54:14 GMT 2025`
Record UNII	45AD6X575G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALVOCIDIB

Official Name

English

FLAVOPIRIDOL

Preferred Name

English

ALVOCIDIB [USAN]

Common Name

English

FLAVOPIRIDOL [MI]

Common Name

English

4H-1-BENZOPYRAN-4-ONE, 2-(2-CHLOROPHENYL)-5,7-DIHYDROXY-8-((3S,4R)-3-HYDROXY-1-METHYL-4-PIPERIDINYL)-

Systematic Name

English

(-)-CIS-2-(2-CHLOROPHENYL)-5,7-DIHYDROXY-8-(3-HYDROXY-1-METHYLPIPERIDIN-4-YL)-4H-1-BENZOPYRAN-4-ONE

Systematic Name

English

L86-8275

Code

English

ALVOCIDIB FREEBASE

Common Name

English

ALVOCIDIB [MART.]

Common Name

English

Alvocidib [WHO-DD]

Common Name

English

alvocidib [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

239607