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Details

Stereochemistry ACHIRAL
Molecular Formula C29H31N7O
Molecular Weight 493.6038
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IMATINIB

SMILES

Cc1ccc(cc1Nc2nccc(-c3cccnc3)n2)NC(=O)c4ccc(cc4)CN5CCN(C)CC5

InChI

InChIKey=KTUFNOKKBVMGRW-UHFFFAOYSA-N
InChI=1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/2009892

Imatinib (GLEEVEC®) is a tyrosine kinase inhibitor and antineoplastic agent that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive CML. Imatinib (GLEEVEC®) inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib (GLEEVEC®) inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

CNS Activity

Curator's Comment:: Imatinib poorly penetrates the blood-brain barrier and has limited activity against CNS leukaemia.

Originator

Curator's Comment:: # Ciba-Geigy Ltd. (now Novartis)

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GLEEVEC

Approved Use

Gleevec is a kinase inhibitor indicated for the treatment of: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (1.1) Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.3) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy (1.4) Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6) Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) (1.9) Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10) 1.1 Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia. 1.4 Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements. 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown. 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. 1.9 Kit+ Gastrointestinal Stromal Tumors (GIST) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. 1.10 Adjuvant Treatment of GIST Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Launch Date

9.8945283E11
Primary
GLEEVEC

Approved Use

Gleevec is a kinase inhibitor indicated for the treatment of: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (1.1) Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.3) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy (1.4) Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6) Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) (1.9) Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10) 1.1 Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia. 1.4 Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements. 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown. 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. 1.9 Kit+ Gastrointestinal Stromal Tumors (GIST) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. 1.10 Adjuvant Treatment of GIST Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Launch Date

9.8945283E11
Primary
GLEEVEC

Approved Use

Gleevec is a kinase inhibitor indicated for the treatment of: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (1.1) Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.3) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy (1.4) Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6) Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) (1.9) Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10) 1.1 Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia. 1.4 Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements. 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown. 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. 1.9 Kit+ Gastrointestinal Stromal Tumors (GIST) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. 1.10 Adjuvant Treatment of GIST Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Launch Date

9.8945283E11
Primary
GLEEVEC

Approved Use

Gleevec is a kinase inhibitor indicated for the treatment of: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (1.1) Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.3) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy (1.4) Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6) Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) (1.9) Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10) 1.1 Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia. 1.4 Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements. 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown. 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. 1.9 Kit+ Gastrointestinal Stromal Tumors (GIST) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. 1.10 Adjuvant Treatment of GIST Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Launch Date

9.8945283E11
Primary
GLEEVEC

Approved Use

Gleevec is a kinase inhibitor indicated for the treatment of: Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (1.1) Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.3) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy (1.4) Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown (1.6) Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) (1.9) Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST (1.10) 1.1 Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Adult patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia. 1.4 Pediatric patients with Ph+ Acute Lymphoblastic Leukemia (ALL) Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy. 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements. 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown. 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown. 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. 1.9 Kit+ Gastrointestinal Stromal Tumors (GIST) Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. 1.10 Adjuvant Treatment of GIST Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.

Launch Date

9.8945283E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.74 mg/L
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4478 ng/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1907.5 ng/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3508.9 ng/mL
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1907.5 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.82 μg/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.75 μg/mL
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.71 μg/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1.18 μg/mL
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
19.9 mg × h/L
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
174.1 ng × h/mL
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
38.8 ng × h/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
89.9 ng × h/mL
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
38.8 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
63.7 μg × h/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
97.3 μg × h/mL
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.1 μg × h/mL
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
19.7 μg × h/mL
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.8 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
17 h
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
14.8 h
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
15.6 h
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
83.3 h
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
23.6 h
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
50.8 h
600 mg 2 times / day multiple, oral
dose: 600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
10.2 h
500 mg 2 times / day multiple, oral
dose: 500 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CGP-74588 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4%
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4%
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4%
600 mg 1 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5%
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IMATINIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
500 mg 2 times / day steady, oral
MTD
Dose: 500 mg, 2 times / day
Route: oral
Route: steady
Dose: 500 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
400 mg 2 times / day steady, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
DLT: Transaminases increased...
Dose limiting toxicities:
Transaminases increased (grade 3, 1 patient)
Sources:
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
DLT: Neutropenia, Hypocalcemia...
Dose limiting toxicities:
Neutropenia (grade 3, 2 patients)
Hypocalcemia (grade 4, 2 patients)
Hypophosphatemia (grade 4, 2 patients)
Hypokalemia (grade 3, 2 patients)
Nausea (grade 3, 2 patients)
Emesis (grade 3, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Transaminases increased grade 3, 1 patient
DLT
400 mg 2 times / day steady, oral
Dose: 400 mg, 2 times / day
Route: oral
Route: steady
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Emesis grade 3, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Hypokalemia grade 3, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Nausea grade 3, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Neutropenia grade 3, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Hypocalcemia grade 4, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
Hypophosphatemia grade 4, 2 patients
DLT
600 mg 2 times / day steady, oral
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 53.3 years (range: 29.8–69.9 years)
n = 35
Health Status: unhealthy
Condition: malignant glioma
Age Group: 53.3 years (range: 29.8–69.9 years)
Sex: M+F
Population Size: 35
Sources:
OverviewDrug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Mechanisms of transformation by the BCR/ABL oncogene.
2001 Apr
Leukemia cells fall on their swords.
2001 Apr
ARG tyrosine kinase activity is inhibited by STI571.
2001 Apr 15
Targeting protein kinases for tumor therapy.
2001 Aug
PDGF-beta receptor expression in the dorsocaudal brainstem parallels hypoxic ventilatory depression in the developing rat.
2001 Aug
STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.
2001 Aug 16
Cutaneous reactions to STI571.
2001 Aug 23
Mechanisms of resistance to imatinib (STI571) and prospects for combination with conventional chemotherapeutic agents.
2001 Feb
Cotreatment with STI-571 enhances tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL or apo-2L)-induced apoptosis of Bcr-Abl-positive human acute leukemia cells.
2001 Feb
Implications of imatinib mesylate for hematopoietic stem cell transplantation.
2001 Jul
Signal transduction inhibition: results from phase I clinical trials in chronic myeloid leukemia.
2001 Jul
Clinical trials referral resource. ST1571.
2001 Jul
Chronic myelogenous leukaemia--new therapeutic principles.
2001 Jul
STI571 revolution: can the newer targeted drugs measure up?
2001 Jul 4
From the Food and Drug Administration.
2001 Jul 4
Tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: so far so good?
2001 Jun
Quick success for cancer kinase treatment.
2001 Jun
Researchers optimistic about sea change in cancer treatment.
2001 Jun 13
Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted therapy of cancer.
2001 Mar
In vivo PDGF beta receptor activation in the dorsocaudal brainstem of the rat prevents hypoxia-induced apoptosis via activation of Akt and BAD.
2001 Mar 23
In search of the silver bullet.
2001 May 14
STI571: a magic bullet?
2001 Oct
Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein.
2001 Sep
Cancer in the crosshairs.
2001 Sep
[Chronic myeloid leukemia and tyrosine kinase inhibitors].
2001 Sep
Small molecule: large hopes.
2001 Sep-Oct
Patents

Sample Use Guides

The prescribed dose should be administered orally, with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
Route of Administration: Oral
In Vitro Use Guide
Imatinib (CGP 57148) was tested for growth inhibition of EGF-dependent BALB/MK cells, the H-ras-transformed T24 bladder carcinoma line, and IL-3-dependent growth of FDC-Pl cells. The compound showed only weak antiproliferative activity against these cell lines, with IC50 values of 12.7 uM, 9.4 uM, and 29.2 uM, respectively. However, when tested on v-abl-transformed PB-3c cells, incubation with CGP 57148 resulted in potent growth inhibition even in the presence of exogenous IL-3 (IC50 values, 0.11 uM without IL-3 and 0.9 uM with IL-3). Similar results were obtained using v-sis-transformed BALB/c 3T3 cells, which grow in response to autocrine PDGF production (IC50, 0.33 uM).
Name Type Language
IMATINIB
EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
IMATINIB [WHO-DD]
Common Name English
NSC-743414
Code English
GLAMOX
Brand Name English
NSC-759854
Code English
IMATINIB [VANDF]
Common Name English
IMATINIB [MI]
Common Name English
IMATINIB [INN]
Common Name English
BENZAMIDE, 4-((4-METHYL-1-PIPERAZINYL)METHYL)-N-(4-METHYL-3-((4-(3-PYRIDINYL)-2-PYRIMIDINYL)AMINOPHENYL)-
Common Name English
IMATINIB [EMA EPAR]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XE01
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EMA ASSESSMENT REPORTS IMANTINIB TEVA (AUTHORIZED: LEUKEMIA, , MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
FDA ORPHAN DRUG 787520
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
LIVERTOX 500
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EU-Orphan Drug EU/3/14/1357
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
FDA ORPHAN DRUG 208905
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
NDF-RT N0000175076
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
NCI_THESAURUS C155700
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
FDA ORPHAN DRUG 303810
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EMA ASSESSMENT REPORTS IMANTINIB ACTAVIS (AUTHORIZED: LEUKEMIA, , MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EMA ASSESSMENT REPORTS GLIVEC (AUTHORIZED: GASTROINTESTINAL STROMAL TUMORS)
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EMA ASSESSMENT REPORTS IMATINIB MEDAC (AUTHORIZED DERMATOFIBROSARCOMA)
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
FDA ORPHAN DRUG 140100
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
EMA ASSESSMENT REPORTS IMANTIB ACCORD (AUTHORIZED: DERMATOFIBROSARCOMA)
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
WHO-VATC QL01XE01
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
Code System Code Type Description
DRUG BANK
DB00619
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
PUBCHEM
5291
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
MESH
C097613
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
EVMPD
SUB25387
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
LACTMED
Imatinib
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
EPA CompTox
152459-95-5
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
RXCUI
282388
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
IMATINIB
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
INN
8031
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
NCI_THESAURUS
C62035
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
MERCK INDEX
M6213
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY Merck Index
IUPHAR
5687
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
ChEMBL
CHEMBL941
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
FDA UNII
BKJ8M8G5HI
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
DRUG CENTRAL
1423
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY
CAS
152459-95-5
Created by admin on Fri Jun 25 21:31:47 UTC 2021 , Edited by admin on Fri Jun 25 21:31:47 UTC 2021
PRIMARY