Home Cell Cycle CDK inhibitor Flavopiridol (Alvocidib) HCl

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Flavopiridol (Alvocidib) HCl CDK inhibitor

Cat.No.S2679

Flavopiridol (Alvocidib) HCl competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM in cell-free assays. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Flavopiridol HCl induces autophagy and ER stress. Flavopiridol HCl blocks HIV-1 replication. Phase 1/2.
Flavopiridol (Alvocidib) HCl CDK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 438.3

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Quality Control

Batch: Purity: 99.44%
99.44

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MCF-7 tumor cell Proliferation assay Inhibition of MCF-7 tumor cell proliferation 10843211
Mia PaCa-2 cell Function assay Inhibition of Mia PaCa-2 cell clonogenic assay, IC50=36 μM 11063609
A2780 cell Function assay Inhibition of A2780 cell clonogenic assay， IC50=15 μM 11063609
HCT116 cell Function assay Inhibition of HCT116 cell clonogenic assay, IC50=13 μM 11063609
PC3 cell Function assay Inhibition of PC3 cell clonogenic assay, IC50=10 μM 11063609
K562 human leukemia cell Proliferation assay Inhibition of K562 human leukemia cell proliferation, IC50=0.13 μM 12190313
MIP human colon carcinoma cell Function assay Inhibition of MIP human colon carcinoma cell line, IC50=0.12 μM 12190313
A549 human lung carcinoma cell Proliferation assay Inhibition of A549 human lung carcinoma cell proliferation, IC50=96 nM 12190313
CACO-2 human colon carcinoma cell Proliferation assay Inhibition of CACO-2 human colon carcinoma cell proliferation, IC50=86 nM 12190313
M109 mouse lung carcinoma cell Proliferation assay Inhibition of M109 mouse lung carcinoma cell proliferation, IC50=80 nM 12190313
A2780/TAX-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-R human ovarian carcinoma cell proliferation, IC50=78 nM 12190313
SKBR-3 human breast carcinoma cell Proliferation assay Inhibition of SKBR-3 human breast carcinoma cell proliferation, IC50=77 nM 12190313
A431 human squamous cell Proliferation assay Inhibition of A431 human squamous cell carcinoma cell proliferation, IC50=75 nM 12190313
LX-1 human lung carcinoma Proliferation assay Inhibition of LX-1 human lung carcinoma proliferation, IC50=75 nM 12190313
MLF mouse lung fibroblast cell Proliferation assay Inhibition of MLF mouse lung fibroblast cell proliferation, IC50=72 nM 12190313
PC3 human prostate carcinoma cell Proliferation assay Inhibition of PC3 human prostate carcinoma cell proliferation, IC50=66 nM 12190313
MCF-7 human breast carcinoma cell Proliferation assay Inhibition of MCF-7 human breast carcinoma cell proliferation, IC50=66 nM 12190313
LS174T human colon carcinoma cell Proliferation assay Inhibition of LS174T human colon carcinoma cell proliferation, IC50=65 nM 12190313
A2780/TAX-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/TAX-S human ovarian carcinoma cell proliferation, IC50=65 nM 12190313
A2780/DDP-S human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-S human ovarian carcinoma cell proliferation, IC50=56 nM 12190313
OVCAR-3 human ovarian carcinoma cell Proliferation assay Inhibition of OVCAR-3 human ovarian carcinoma cell proliferation, IC50=54 nM 12190313
CCRF-CEM human leukemia cell Proliferation assay Inhibition of CCRF-CEM human leukemia cell proliferation, IC50=52 nM 12190313
Hs 27 human fibroblast cell Proliferation assay Inhibition of Hs 27 human fibroblast cell proliferation, IC50=51 nM 12190313
HL60 human leukemia cell Proliferation assay Inhibition of HL60 human leukemia cell proliferation, IC50=46 nM 12190313
ABAE human fibroblast cell Proliferation assay Inhibition of ABAE human fibroblast cell proliferation, IC50=45 nM 12190313
A2780/DDP-R human ovarian carcinoma cell Proliferation assay Inhibition of A2780/DDP-R human ovarian carcinoma cell proliferation, IC50=38 nM 12190313
HCT116/VM46 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VM46 human colon carcinoma cell proliferation, IC50=21 nM 12190313
HCT116 human colon carcinoma cell Proliferation assay Inhibition of HCT116 human colon carcinoma cell proliferation, IC50=18 nM 12190313
HCT116/VP35 human colon carcinoma cell Proliferation assay Inhibition of HCT116/VP35 human colon carcinoma cell proliferation, IC50=17 nM 12190313
LNCaP human prostate carcinoma cell Proliferation assay Inhibition of LNCaP human prostate carcinoma cell proliferation 12190313
human A2780 cell line Proliferation assay 72 h Antiproliferative effect against human A2780 cell line was determined in a whole cell 72 hr cytotoxicity assay, IC50=71 nM 15027863
human ovarian (A2780) cancer cell Cytotoxic assay Cytotoxic effect on human ovarian (A2780) cancer cell line, IC50=71 nM 15125971
ID8 Antiproliferative activity against Antiproliferative activity against ID8 cells, IC50=0.007μM 17123821
MCF7 Antiproliferative activity against Antiproliferative activity against MCF7 cells, IC50=0.026μM 17123821
Sf9 Inhibition of recombinant cyclin A/CDK2 expressed in Inhibition of recombinant cyclin A/CDK2 expressed in Sf9 cells, IC50=0.012μM 17904366
A2780 Inhibition of cdk-mediated NPM phosphorylation at Inhibition of cdk-mediated NPM phosphorylation at thr199 in human A2780 cells 18469809
A2780 Inhibition of cdk-mediated Rb phosphorylation at 24 hrs Inhibition of cdk-mediated Rb phosphorylation at thr821 in human A2780 cells after 24 hrs 18469809
A2780 Inhibition of cdk-mediated Rb phosphorylation at 24 hrs Inhibition of cdk-mediated Rb phosphorylation at ser807/811 in human A2780 cells after 24 hrs 18469809
A2780 Inhibition of cdk9-mediated RNA pol2 CTD phosphorylation at 24 hrs Inhibition of cdk9-mediated RNA pol2 CTD phosphorylation at ser2 in human A2780 cells after 24 hrs 18469809
A2780 Inhibition of cdk7-mediated RNA pol2 CTD phosphorylation at 24 hrs Inhibition of cdk7-mediated RNA pol2 CTD phosphorylation at ser5 in human A2780 cells after 24 hrs 18469809
A2780 Induction of apoptosis in 24 hrs Induction of apoptosis in human A2780 cells assessed as appearance of Mcl1 protein level after 24 hrs 18469809
NCI60 Antiproliferative activity against 72 hrs Antiproliferative activity against human NCI60 cells after 72 hrs by sulforhodamine B assay, GI50=0.0747μM 21080703
NCI60 Antiproliferative activity against 72 hrs Antiproliferative activity against human NCI60 cells assessed as lethal effect after 72 hrs by sulforhodamine B assay, LC50=0.904μM 21080703
DR-U2OS-GFP Reduction of homologous recombination in 0.1 uM 56 hrs Reduction of homologous recombination in human DR-U2OS-GFP cells expressing I-SceI nuclease assessed as reduction of RAD51 level at 0.1 uM after 56 hrs by immunoblotting 21417417
A2780 Cytotoxicity against 24 hrs Cytotoxicity against human A2780 cells after 24 hrs by MTT assay, GI50=0.023μM 23301767
MRC5 Cytotoxicity against 72 hrs Cytotoxicity against human MRC5 cells after 72 hrs by MTT assay, GI50=0.028μM 23301767
A2780 Cytotoxicity against 72 hrs Cytotoxicity against human A2780 cells after 72 hrs by MTT assay, GI50=0.029μM 23301767
A2780 Cytotoxicity against 48 hrs Cytotoxicity against human A2780 cells after 48 hrs by MTT assay, GI50=0.031μM 23301767
MRC5 Cytotoxicity against 48 hrs Cytotoxicity against human MRC5 cells after 48 hrs by MTT assay, GI50=0.039μM 23301767
MRC5 Cytotoxicity against 24 hrs Cytotoxicity against human MRC5 cells after 24 hrs by MTT assay, GI50=0.049μM 23301767
HMEC1 Cytotoxicity against 24 hrs Cytotoxicity against human HMEC1 cells after 24 hrs by MTT assay, GI50=0.061μM 23301767
HMEC1 Cytotoxicity against 48 hrs Cytotoxicity against human HMEC1 cells after 48 hrs by MTT assay, GI50=0.062μM 23301767
HMEC1 Cytotoxicity against 72 hrs Cytotoxicity against human HMEC1 cells after 72 hrs by MTT assay, GI50=0.066μM 23301767
A2780 Inhibition of CDK9 in 24 hrs Inhibition of CDK9 in human A2780 cells assessed as reduction of RNAPII CTD phosphorylation at Ser2 at GI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Cell cycle arrest in 24 hrs Cell cycle arrest in human A2780 cells assessed as accumulation at G2/M phase at less than GI50 after 24 hrs by flow cytometric analysis 23301767
A2780 Inhibition of CDK9 in 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of MCL1 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Inhibition of CDK9 in 24 hrs Inhibition of CDK9 in human A2780 cells assessed as downregulation of HDM2 at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
A2780 Induction of apoptosis in 24 hrs Induction of apoptosis in human A2780 cells assessed as induction of PARP cleavage at GI50 to 5XGI50 concentration after 24 hrs by Western blotting analysis 23301767
MT4 Antiviral activity against Antiviral activity against Human immunodeficiency virus 1 NL 4-3 infected in MT4 cells measured on day 4 post infection by p24 assay, EC50=0.015μM 25914804
MT4 Cytotoxicity against Cytotoxicity against human MT4 cells, IC50=0.067μM 25914804
Sf9 Inhibition of CDK2/cyclin E1 (unknown origin) expressed in 15 mins Inhibition of CDK2/cyclin E1 (unknown origin) expressed in Sf9 insect cells using UlightCFFKNIVTPRTPPPSQGK-amide substrate after 15 mins by autoradiography, IC50=0.13μM 25914804
A549 Antiproliferative activity against 3 days Antiproliferative activity against human A549 cells after 3 days by SRB method, GI50=0.14μM 25914804
DU145 Antiproliferative activity against 3 days Antiproliferative activity against human DU145 cells after 3 days by SRB method, GI50=0.15μM 25914804
KB Antiproliferative activity against 3 days Antiproliferative activity against human KB cells after 3 days by SRB method, GI50=0.16μM 25914804
KBVIN Antiproliferative activity against 3 days Antiproliferative activity against human KBVIN cells after 3 days by SRB method, GI50=0.18μM 25914804
HCT116 Antiproliferative activity against 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 10% fetal bovine serum, EC50=0.034μM 26985305
HCT116 Antiproliferative activity against 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Celltiter-Glo reagent based assay in presence of 0.625% fetal bovine serum, EC50=0.059μM 26985305
Sf9 Inhibition of human 10 mins Inhibition of human His6-tagged CDK9/cyclin T1 expressed in baculovirus infected sf9 cells using GST-CTD as substrate after 10 mins in presence of [gamma-32P]ATP by SDS-PAGE analysis, IC50=0.0025μM 27171036
Sf21 Inhibition of recombinant human Inhibition of recombinant human full length C-terminal His6-tagged CDK9/cyclin T1 expressed in baculovirus infected Sf21 insect cells using PDKtide as substrate, IC50=0.011μM 27171036
HeLa Cytotoxicity against 72 hrs Cytotoxicity against human HeLa cells assessed as decrease in cell viability after 72 hrs by MTT assay, CC50=0.12μM 27171036
Sf21 Inhibition of full length human Inhibition of full length human N-terminal His6-tagged CDK6/N-terminal GST-tagged cyclin D3 expressed in sf21 cells using histone H1 substrate, IC50=0.395μM 27171036
Sf21 Inhibition of recombinant human Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, IC50=0.514μM 27171036
HCT116 Antiproliferative activity against 72 hrs Antiproliferative activity against human HCT116 cells assessed as growth inhibition in presence of 0.625% FBS after 72 hrs, EC50=0.059μM 27326333
HepG2 Antiproliferative activity against 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by CelTiter-Glo assay, EC50=0.1464μM 29407975
KOPN8 Antiproliferative activity against 72 hrs Antiproliferative activity against human KOPN8 cells after 72 hrs by CelTiter-Glo assay, EC50=0.1926μM 29407975
SEM Antiproliferative activity against 72 hrs Antiproliferative activity against human SEM cells after 72 hrs by CelTiter-Glo assay, EC50=0.2043μM 29407975
UOCB1 Antiproliferative activity against 72 hrs Antiproliferative activity against human UOCB1 cells after 72 hrs by CelTiter-Glo assay, EC50=0.2084μM 29407975
KOPN8 Induction of apoptosis in 0.5 uM 3 to 24 hrs Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM after 3 to 24 hrs by Western blot analysis 29407975
KOPN8 Induction of apoptosis in 0.5 uM 1 hr Induction of apoptosis in human KOPN8 cells assessed as upregulation of cleaved PARP level at 0.5 uM pre-treated with NAC for 1 hr and measured after 3 to 24 hrs by Western blot analysis 29407975
insect cells Inhibition of human 2.5 mins Inhibition of human CDK4/cyclin D1 expressed in insect cells after 2.5 mins by liquid scintillation counting analysis, IC50=0.02μM 30733087
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Caco-2 Toxicity assay 48 hrs Toxicity against Caco-2 cells determined at 48 hours by intracellular ATP concentration using the CellTiter-Glo Luminescent Cell Viability Assay, CC50=0.06μM ChEMBL
Caco-2 Function assay 48 hrs Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50=0.59μM ChEMBL
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Solubility

In vitro
Batch:

DMSO : 88 mg/mL (200.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 37 mg/mL

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
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Chemical Information, Storage & Stability

Molecular Weight 438.3 Formula

C21H20ClNO5.HCl

 Storage (From the date of receipt)
CAS No. 131740-09-5 Download SDF Storage of Stock Solutions

Synonyms NSC 649890, L86-8275, HMR-1275, DSP-2033 Smiles CN1CCC(C(C1)O)C2=C(C=C(C3=C2OC(=CC3=O)C4=CC=CC=C4Cl)O)O.Cl

Mechanism of Action

Targets/IC50/Ki
CDK1
(Cell-free assay)
40 nM
CDK2
(Cell-free assay)
40 nM
CDK4
(Cell-free assay)
40 nM
CDK6
(Cell-free assay)
40 nM
CDK7
(Cell-free assay)
300 nM
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.
Kinase Assay
Recombinant CDKs Kinase Reactions
CDKs activities are determined in microtiter plates as follows. Forty μg Gst-Rb are mixed with different amounts of Flavopiridol and unlabeled ATP. Reactions are then started by the addition of an ammonium sulfate cut of the S100 fraction obtained from insect cells expressing recombinant human CDKs. The final reaction conditions are 10 mM MgCl2, 50 mM Tris-HCl (pH 7.5), and 1 mM DTT. The final concentration of ATP is adjusted accordingly. Radiolabeled ATP is used as a phosphoryl donor. The reaction is carried out for 2.5 minutes at 30 °C after addition of enzyme and then terminated with the addition of EDTA. The Gst-Rb is then captured with glutathione-Sepharose and the incorporated radioactivity is determined by liquid scintillation counting.
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
  • [4] https://pubmed.ncbi.nlm.nih.gov/9815683/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22391209/
  • [6] https://pubmed.ncbi.nlm.nih.gov/9516149/

Applications

Methods Biomarkers Images PMID
Western blot CDK2 / CDK4 / Cyclin A / p21 / p27 / Rb p-ERK / ERK / p-p38 / p-4EBP1 / 4EBP1 / p-S6 p-RNAPII / p-eIF4E / Mnk1 Cleaved caspase-8 / Cleaved caspase-9 / Cleaved caspase-3
S2679-WB4
24572052
Growth inhibition assay Cell viability
S2679-viability1
31193061

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00112723 Terminated
Adult Lymphocyte Depletion Hodgkin Lymphoma|Adult Lymphocyte Predominant Hodgkin Lymphoma|Adult Mixed Cellularity Hodgkin Lymphoma|Adult Nodular Sclerosis Hodgkin Lymphoma|Anaplastic Large Cell Lymphoma|Angioimmunoblastic T-cell Lymphoma|Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue|Nodal Marginal Zone B-cell Lymphoma|Recurrent Adult Diffuse Large Cell Lymphoma|Recurrent Adult Diffuse Mixed Cell Lymphoma|Recurrent Adult Diffuse Small Cleaved Cell Lymphoma|Recurrent Adult Grade III Lymphomatoid Granulomatosis|Recurrent Adult Hodgkin Lymphoma|Recurrent Adult T-cell Leukemia/Lymphoma|Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma|Recurrent Grade 1 Follicular Lymphoma|Recurrent Grade 2 Follicular Lymphoma|Recurrent Grade 3 Follicular Lymphoma|Recurrent Mantle Cell Lymphoma|Recurrent Marginal Zone Lymphoma|Recurrent Mycosis Fungoides/Sezary Syndrome|Recurrent Small Lymphocytic Lymphoma|Refractory Multiple Myeloma|Splenic Marginal Zone Lymphoma|Stage I Multiple Myeloma|Stage II Multiple Myeloma|Stage III Multiple Myeloma|Waldenström Macroglobulinemia
National Cancer Institute (NCI)
 December 2005 Phase 1|Phase 2
NCT00098371 Terminated
B-cell Chronic Lymphocytic Leukemia|Prolymphocytic Leukemia|Refractory Chronic Lymphocytic Leukemia
National Cancer Institute (NCI)
 April 2005 Phase 2
NCT00101231 Terminated
Adult Acute Basophilic Leukemia|Adult Acute Eosinophilic Leukemia|Adult Acute Megakaryoblastic Leukemia (M7)|Adult Acute Minimally Differentiated Myeloid Leukemia (M0)|Adult Acute Monoblastic Leukemia (M5a)|Adult Acute Monocytic Leukemia (M5b)|Adult Acute Myeloblastic Leukemia With Maturation (M2)|Adult Acute Myeloblastic Leukemia Without Maturation (M1)|Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities|Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)|Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)|Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)|Adult Acute Myelomonocytic Leukemia (M4)|Adult Erythroleukemia (M6a)|Adult Pure Erythroid Leukemia (M6b)|Blastic Phase Chronic Myelogenous Leukemia|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent Adult Acute Myeloid Leukemia|Relapsing Chronic Myelogenous Leukemia
National Cancer Institute (NCI)
 October 2004 Phase 1
NCT00058240 Completed
B-cell Chronic Lymphocytic Leukemia|Recurrent Small Lymphocytic Lymphoma|Refractory Chronic Lymphocytic Leukemia|Waldenström Macroglobulinemia
National Cancer Institute (NCI)
 April 2003 Phase 1|Phase 2

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