c-Kit (IC50 ~100 nM); Bcr-Abl (IC50 ~100 nM); PDGFR (IC50 ~100 nM)

Imatinib (STI571) Mesylate prevents c-Kit autophosphorylation, MAPK activation, and Akt activation without changing the overall amounts of c-kit, MAPK, or Akt protein. About 100 nM is the concentration that results in 50% inhibition for these effects[1]. The kinase Bcr-Abl that causes chronic myeloid leukemia is highly susceptible to imatinib (STI571) mesylate (in vitro IC50 of 25 nM). Moreover, imatinib effectively inhibits PDGFR (in vitro IC50, 380 nM) and Kit (in vitro IC50, 410 nM)[2]. Imatinib (STI571) mesylate is a multi-target inhibitor of v-Abl, c-Kit, and it also inhibits the native PDGFβ receptor, Bcr/Abl, v-Abl, Tel/Abl, and c-Kit. However, it does not inhibit the EGFR, c-Fms, Flt3, Src family kinases, or numerous other tyrosine kinases. Imatinib has no effect on untransformed Ba/F3 cells growing in IL-3 or on Ba/F3 cells transformed by Tel/JAK2[3]. However, it inhibits the tyrosine phosphorylation and cell growth of Ba/F3 cells expressing Bcr/Abl, Tel/Abl, Tel/PDGFβR, and Tel/Arg with an IC50 of approximately 0.5 μM in each case. Imatinib mesylate specifically impedes c-Kit, PDGFR kinase, and Bcr/Abl activity. In patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML), imatinib mesylate exhibits unique and swift antileukemic activity[4].

Imatinib has varying antitumor effects on three xenografted tumors made from surgical samples of newly diagnosed human small cell lung cancers: the growth of the SCLC6, SCLC61, and SCLC108 tumors is inhibited by 80%, 40%, and 78%, respectively, while the growth of SCLC74 is not significantly affected. When administered by gavage at 10, 20, and 40 mg/kg, respectively, Imatinib significantly reduces the high fat-induced lipid staining area in ApoE(-/-) mice fed a high fat diet by 30%, 27%, and 35% compared to high fat diet untreated controls and suppresses carotid artery lipid accumulation.

Rabbit antiserum is used to immunoprecipitate the PDGF receptor from extracts of BALB/c 3T3 cells, which is then left on ice for two hours. Antigen-antibody complexes are gathered using protein A-Sepharose beads. TNET (50 mM Tris, pH 7.5, 140 mM NaCl, 5 mM EDTA, 1% Triton X-100), TNE (50 mM Tris, pH 7.5, 140 mM EDTA), and kinase buffer (20 mM Tris, pH 7.5, 10 mM MgCl2) are the three solutions used to wash the immunoprecipitates twice. A variety of drug concentrations are added to the reaction mixture after PDGF (50 ng/mL) stimulation for 10 minutes at 4°C.

Twenty-four hours before the test compounds are added, tested A549 cells are arranged at a density of 5×10³ cells per well in 96-well flat-bottom plates. In addition to different doses of Imatinib mesylate (10, 100, 1000, and 10,000 ng/mL) and other cytostatic medications (Docetaxel (DTX) or Idarubicin (ID): 0.1, 1, 10, 100 ng/mL; Cisplatin (CIS): 1, 10, 100, 1000 ng/mL), the cells are incubated with PRI-2191 at two different concentrations (10 and 100 nM) for 96 hours. The assay known as sulforhodamine B (SRB) is utilized to assess the cytotoxic effect. As a result, the Dmitry Nevozhay software Cheburator 0.4 calculates the IC50 for every individual experiment[4].

Mice: We use female NOD/SCID mice that are 12–16 weeks old and weigh 20–25 g. On Day 0, mice receive a subcutaneous (s.c.) inoculation of A549 tumor cells suspension (5×10⁶ cells in 0.2 mL of Hank's medium per mouse). Following this, they are randomly assigned to groups that receive different combinations of vitamin D analogs and chemotherapeutics. In the corresponding experiments, one of the two experimental protocols is used: 1. After the tumor cells are injected, treatment begins on Day 7 (when the tumors become palpable). For 19 days (from Days 7 to 25), imatinib mesylate is given intraperitoneally (i.p.) at a dose of 75 mg/kg/day. PRI-2191 is given orally or s.c. three times a week (on Days 7, 12, 14, 16, 19, 21, and 23) at a dose of 2 μg/kg/day. 2. After tumor cells are injected, treatment begins on Day 7 (when tumors become palpable). For 13 days (from Days 7-19), imatinib mesylate is given intraperitoneally (i.p.) at a dose of 50 mg/kg/day. PRI-2191 and PRI-2205 are given subcutaneously (s.c.) three times a week (on Days 7, 10, 12, 14, 17, 19, 21, 24, and 26) at doses of 1 or 10 μg/kg/day, respectively. Blood is drawn while the mice are sedated at the conclusion of the trials, and they are then killed.
Rats: In the experiments, male Lewis rats weighing between 270 and 320 g are employed. The Imatinib group (n = 7) receives an intraperitoneal injection of Imatinib mesylate (50 mg/kg), while the vehicle group (n = 7) receives 0.5 mL of 20% DMSO without Imatinib. Preliminary testing reveals that the 25 mg/kg dose slightly improves lung function without reaching statistical significance. Based on previous reports and this result, the intraperitoneal administration of 50 mg/kg was chosen. The animals have a left thoracotomy, and a tiny metallic clamp is used to occlude the left hilum. The occlusion is carried out 20 minutes following the administration of imatinib or the vehicle. Tidal volume (TV) and respiratory rate (RR) are set to 8 mL/kg and 80 breaths/min, respectively, during clamping. The clamp is taken off after 90 minutes of ischemia, and reperfusion is sustained for an additional 120 minutes. The bilateral lung's blood flow and ventilation are restored during reperfusion. The animals in the sham group (n=6) undergo 210 minutes of ventilation, thoracotomy, and heparinization.

Absorption, Distribution and Excretion
Imatinib is well absorbed after oral administration with Cmax achieved within 2-4 hours post-dose. Mean absolute bioavailability for the capsule formulation is 98%. Following oral administration in healthy volunteers, the elimination half-lives of imitanib and its major active metabolite, the N-desmethyl derivative, were approximately 18 and 40 hours, respectively. Mean imatinib AUC increased proportionally with increasing dose in the range 25 mg-1000 mg. There was no signficant change in the pharmacokinetics of imatinib on repeated dosing, and accumulation is 1.5-2.5 fold at steady state when Gleevec is dosed once daily. At clinically relevant concentrations of imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and (alpha)1-acid glycoprotein.
Fecal /elimination/ - 68% within 7 days (20% of dose unchanged); Renal /elimination/ - 13% within 7 days (5% of dose unchanged).
Typically, clearance of imitanib in a 50-year-old patient weighing 50 kg is expected to be 8 L/hr, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/hr. However, the inter-patient variability of 40% in clearance does not warrant initial dose adjustment based on body weight and/or age but indicates the need for close monitoring for treatment related toxicity.
In lactating female rats administered 100 mg/kg ... imatinib and/or its metabolites were extensively excreted in milk. It is estimated that approximately 1.% of a maternal dose is excreted into milk, which is equivalent to a dose to the infant of 30% the maternal dose per unit body weight.

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Metabolism / Metabolites
CYP3A4 is the major enzyme responsible for metabolism of imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to imatinib. The plasma AUC for this metabolite is about 15% of the AUC for imatinib.

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Biological Half-Life
Elimination - Approximately 18 and 40 hours, for imatinib and its primary metabolite, respectively.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that maternal doses of imatinib up to 400 mg daily produce low levels of the drug and its active metabolite in milk. Although a few breastfed infants apparently experienced no adverse effects during maternal use of imatinib, no long-term data are available. Until more data are available, imatinib should be used only with careful monitoring during breastfeeding. National Comprehensive Cancer Network guidelines, the manufacturer and some authors recommend that breastfeeding be discontinued during imatinib therapy and for 1 month after therapy.
◉ Effects in Breastfed Infants
A woman receiving oral imatinib 400 mg daily for chronic myeloid leukemia breastfed her infant. No adverse effects were noted in the infant during the first 2 months of nursing.
One woman with chronic myelogenous leukemia received imatinib 400 mg daily throughout pregnancy and during breastfeeding (extent not stated) for nearly 6 months postpartum. Her infant reportedly grew and developed normally.
A woman with chronic myeloid leukemia received imatinib 400 mg daily starting at week 8 of pregnancy and continuing throughout 8 months of breastfeeding (extent not stated). The infant was healthy, but an atrial septal defect was repaired at 30 months of age. It was thought to be unrelated to imatinib therapy.
A pregnant woman with Philadelphia chromosome-positive chronic myelogenous leukemia was started on imatinib 400 mg daily during pregnancy. After delivery, her preterm infant was fed colostrum until the middle of the fifth day postpartum when exclusive formula feeding was instituted. The infant was treated for apnea of prematurity and discharged on day 25 of life. No adverse effects on growth or development were noted during the first year of life.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood. 2000 Aug 1;96(3):925-32.

[2]. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9.

[3]. ARG tyrosine kinase activity is inhibited by STI571.Blood. 2001 Apr 15;97(8):2440-8.

[4]. Vitamin D Analogs Potentiate the Antitumor Effect of Imatinib Mesylate in a Human A549 Lung Tumor Model. Int J Mol Sci. 2015 Nov 13;16(11):27191-207.

[5]. Protective Effects of Imatinib on Ischemia/Reperfusion Injury in Rat Lung. Ann Thorac Surg. 2016 Jul 23. pii: S0003-4975(16)30523-9.

[6]. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183.

Imatinib methanesulfonate is a methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours. It has a role as an antineoplastic agent, an apoptosis inducer, a tyrosine kinase inhibitor and an anticoronaviral agent. It contains an imatinib.
Imatinib Mesylate is the mesylate salt of imatinib, a tyrosine kinase inhibitor with antineoplastic activity. Imatinib binds to an intracellular pocket located within tyrosine kinases (TK), thereby inhibiting ATP binding and preventing phosphorylation and the subsequent activation of growth receptors and their downstream signal transduction pathways. This agent inhibits TK encoded by the bcr-abl oncogene as well as receptor TKs encoded by the c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Inhibition of the bcr-abl TK results in decreased proliferation and enhanced apoptosis in malignant cells of Philadelphia-positive (Ph+) hematological malignancies such as CML and ALL; effects on c-kit TK activity inhibit mast-cell and cellular proliferation in those diseases overexpressing c-kit, such as mastocytosis and gastrointestinal stromal tumor (GIST).
A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.
See also: Imatinib (has active moiety).

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Drug Indication
Glivec is indicated for the treatment of, , , adult and paediatric patients with newly diagnosed Philadelphia-chromosome (bcr-abl)-positive (Ph+) chronic myeloid leukaemia (CML) for whom bone-marrow transplantation is not considered as the first line of treatment; , adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis; , adult and paediatric patients with newly diagnosed Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy; , adult patients with relapsed or refractory Ph+ ALL as monotherapy; , adult patients with myelodysplastic / myeloproliferative diseases (MDS / MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements; , adult patients with advanced hypereosinophilic syndrome (HES) and / or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRa rearrangement. , , , The effect of Glivec on the outcome of bone-marrow transplantation has not been determined. , , Glivec is indicated for: , , , the treatment of adult patients with Kit (CD 117)-positive unresectable and / or metastatic malignant gastrointestinal stromal tumours (GIST); , the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment; , the treatment of adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and / or metastatic DFSP who are not eligible for surgery. , , , In adult and paediatric patients, the effectiveness of Glivec is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS / MPD, on haematological response rates in HES / CEL and on objective response rates in adult patients with unresectable and / or metastatic GIST and DFSP and on recurrence-free survival in adjuvant GIST. The experience with Glivec in patients with MDS / MPD associated with PDGFR gene re-arrangements is very limited (see section 5. 1). Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases. ,
Imatinib Koanaa is indicated for the treatment ofadult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. adult patients with relapsed or refractory Ph+ ALL as monotherapy. adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement. The effect of Imatinib on the outcome of bone marrow transplantation has not been determined. Imatinib Koanaa is indicated forthe treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST). the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment. the treatment of adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery. In adult and paediatric patients, the effectiveness of Imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in HES/CEL and on objective response rates in adult patients with unresectable and/or metastatic GIST and DFSP and on recurrence-free survival in adjuvant GIST. The experience with Imatinib in patients with MDS/MPD associated with PDGFR gene re-arrangements is very limited (see section 5. 1). Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
Imatinib Accord is indicated for the treatment of- adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. - adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. - adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. - adult patients with relapsed or refractory Ph+ ALL as monotherapy. - adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. - adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement. - adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery. - the treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST). - the adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatmentThe effect of imatinib on the outcome of bone marrow transplantation has not been determined. In adult and paediatric patients, the effectiveness of imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in HES/CEL and on objective response rates in adult patients with unresectable and/or metastatic DFSP. The experience with imatinib in patients with MDS/MPD associated with PDGFR gene re-arrangements is very limited (see section 5. 1). Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.   
Imatinib medac is indicated for the treatment of: paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment; paediatric patients with Ph+CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase; adult and paediatric patients with Ph+CML in blast crisis; adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ALL) integrated with chemotherapy; adult patients with relapsed or refractory Ph+ALL as monotherapy; adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements; adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement; adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery. The effect of imatinib on the outcome of bone marrow transplantation has not been determined. In adult and paediatric patients, the effectiveness of imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ALL, MDS/MPD, on haematological response rates in HES/CEL and on objective response rates in adult patients with unresectable and/or metastatic DFSP. The experience with imatinib in patients with MDS/MPD associated with PDGFR gene re-arrangements is very limited. Except in newly diagnosed chronic phase CML, there are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.
Imatinib Teva B. V. is indicated for the treatment of: , , , Paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment. , Paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy, or in accelerated phase or blast crisis. , Adult patients with Ph+ CML in blast crisis. , Adult and paediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) integrated with chemotherapy. , Adult patients with relapsed or refractory Ph+ ALL as monotherapy. ,  Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements. , Adult patients with advanced hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL) with FIP1L1-PDGFRα rearrangement. , , , The effect of imatinib on the outcome of bone marrow transplantation has not been determined. , , Imatinib Teva B. V. is indicated for: , , , The treatment of adult patients with Kit (CD 117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST). , The adjuvant treatment of adult patients who are at significant risk of relapse following resection of Kit (CD117)-positive GIST. Patients who have a low or very low risk of recurrence should not receive adjuvant treatment. , The treatment of adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic DFSP who are not eligible for surgery. , , , In adult and paediatric patients, the effectiveness of imatinib is based on overall haematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in HES/CEL and on objective response rates in adult patients with unresectable and/or metastatic GIST and DFSP and on recurrence-free survival in adjuvant GIST. The experience with imatinib in patients with MDS/MPD associated with PDGFR gene re-arrangements is very limited. There are no controlled trials demonstrating a clinical benefit or increased survival for these diseases. ,
Dermatofibrosarcoma protuberans, Hypereosinophilic syndrome and/or chronic eosinophilic leukaemia with FIP1L1-platelet-derived growth factor receptor alpha gene re-arrangement, Kit (CD 117)-positive gastrointestinal stromal tumours, Myelodysplastic / myeloproliferative diseases associated with platelet-derived growth factor receptor gene re-arrangements, Philadelphia chromosome (BCR-ABL translocation)-positive acute lymphoblastic leukaemia, Philadelphia chromosome (BCR-ABL translocation)-positive chronic myeloid leukaemia
Treatment of pulmonary arterial hypertension

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Mechanism of Action
Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. In colony formation assays using ex vivo peripheral blood and bone marrow samples, imatinib shows inhibition of Bcr-Abl positive colonies from CML patients.In vivo, it inhibits tumor growth of Bcr-Abl transfected murine myeloid cells as well as Bcr-Abl positive leukemia lines derived from CML patients in blast crisis.
Imatinib 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 inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

C30H35N7O4S

589.71

589.247

C, 61.10; H, 5.98; N, 16.63; O, 10.85; S, 5.44

220127-57-1

Imatinib;152459-95-5;N-Desmethyl imatinib;404844-02-6

123596

white to off-white to brownish or yellowish tinged crystalline powder

0.858 g/mL at 25 °C(lit.)

133-134 °C(lit.)

214-224°C

64°F

n20/D 1.401(lit.)

5.196

3

10

7

42

799

0

S(C([H])([H])[H])(=O)(=O)O[H].O=C(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H])N([H])C1C([H])=C([H])C(C([H])([H])[H])=C(C=1[H])N([H])C1=NC([H])=C([H])C(C2=C([H])N=C([H])C([H])=C2[H])=N1

YLMAHDNUQAMNNX-UHFFFAOYSA-N

InChI=1S/C29H31N7O.CH4O3S/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;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)

methanesulfonic acid;4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide

STI571; CGP-57148B; ST-1571 Mesylate; CGP 57148; CGP57148; CGP-57148; CGP-57148B; CGP57148B; ; STI-571; STI 571; Imatinib mesylate; Brand name: Gleevec (USA); Glivec (other countries)

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: Saline: 30 mg/mL

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Solubility in Formulation 5: 100 mg/mL (169.57 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)