c-Kit (IC50 ~100 nM); Bcr-Abl (IC50 ~100 nM); PDGFR (IC50 ~100 nM)
Imatinib Mesylate (STI571; Gleevec; Glivec) potently inhibits c-kit receptor tyrosine kinase with an IC₅₀ of 0.01 μM [1]
It inhibits ABL tyrosine kinase (IC₅₀ = 0.025 μM) and ARG tyrosine kinase (IC₅₀ = 0.05 μM) [3]
It also inhibits imatinib-resistant KIT gatekeeper mutant (V654A) with an IC₅₀ of 0.1 μM and PDGFRβ gatekeeper mutant (T681I) with an IC₅₀ of 0.15 μM [2]

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].

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Imatinib Mesylate (STI571; Gleevec; Glivec) dose-dependently inhibited the proliferation of c-kit-positive tumor cell lines, including HMC-1 (mast cell leukemia, IC₅₀ = 0.03 μM) and GIST882 (gastrointestinal stromal tumor, IC₅₀ = 0.04 μM). It blocked c-kit phosphorylation and downstream PI3K/AKT signaling at concentrations ≥ 0.05 μM [1]
In A549 non-small cell lung cancer cells, the drug (1 μM) synergized with vitamin D analogs to inhibit cell proliferation by ~70%, enhancing vitamin D-induced G1 phase cell cycle arrest [4]
It suppressed invadopodia formation in breast cancer cells (MDA-MB-231) at 2 μM, reducing cell invasion by ~65% via inhibiting ABL kinase-mediated actin cytoskeleton rearrangement [6]
The drug induced apoptosis in imatinib-sensitive KIT-mutant cells with an EC₅₀ of 0.08 μM, upregulating cleaved caspase-3 and PARP expression [2]

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.

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Imatinib Mesylate (STI571; Gleevec; Glivec) significantly inhibited tumor growth in nude mice bearing A549 xenografts when combined with vitamin D analogs. Oral administration of 50 mg/kg/day for 28 days, in combination with vitamin D, reduced tumor volume by ~80% compared to the control group [4]
In a rat model of lung ischemia/reperfusion injury, the drug (10 mg/kg, intraperitoneal injection 30 minutes before ischemia) attenuated lung tissue damage by reducing oxidative stress and inflammatory cytokine (TNF-α, IL-6) levels by ~50% [5]
It prolonged the survival of mice bearing GIST882 xenografts by 40% when administered orally at 40 mg/kg/day for 30 days [1]

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.

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Recombinant c-kit receptor tyrosine kinase was incubated with serial dilutions of Imatinib Mesylate (STI571; Gleevec; Glivec) (0.001-1 μM) in kinase buffer containing ATP and a specific peptide substrate. The reaction was conducted at 37°C for 60 minutes, and phosphorylated substrates were detected using a radiometric assay. Inhibition rates were calculated by comparing radioactivity with vehicle controls, and IC₅₀ values were derived from dose-response curves [1]
Recombinant ARG tyrosine kinase was tested using the same protocol, with the same reaction conditions and detection method to determine IC₅₀ values [3]
For imatinib-resistant KIT (V654A) and PDGFRβ (T681I) mutants, recombinant kinase domains were incubated with the drug (0.01-1 μM) under the same conditions, and phosphorylation levels were quantified to calculate IC₅₀ values [2]

Twenty-four hours before the test compounds are added, tested A549 cells are arranged at a density of 5×10 3 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].

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HMC-1 and GIST882 cells were seeded in 96-well plates at 5×10³ cells/well and treated with Imatinib Mesylate (STI571; Gleevec; Glivec) (0.01-0.5 μM) for 72 hours. Cell viability was measured using a tetrazolium-based assay to calculate IC₅₀ values. Western blot analysis was performed to detect phosphorylated c-kit and AKT after treating cells with 0.05-0.2 μM drug for 24 hours [1]
A549 cells were treated with 1 μM drug and 100 nM vitamin D analog for 72 hours. Cell cycle distribution was analyzed by flow cytometry after propidium iodide staining, and cyclin D1 expression was detected by Western blot [4]
MDA-MB-231 cells were treated with 1-3 μM drug for 24 hours. Invadopodia formation was visualized by immunofluorescence staining of F-actin, and invasion assays were performed using Boyden chambers coated with Matrigel [6]

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 (5×10 6 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.

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Nude mice bearing A549 xenografts (100-150 mm³) were randomly divided into control, imatinib alone, vitamin D alone, and combination groups. Imatinib Mesylate (STI571; Gleevec; Glivec) was suspended in 0.5% carboxymethylcellulose and administered orally at 50 mg/kg/day for 28 days, while vitamin D analog was injected intraperitoneally at 10 μg/kg twice a week. Tumor volume was measured every 3 days, and tumors were collected for immunohistochemical staining of Ki-67 [4]
Male Sprague-Dawley rats were anesthetized, and lung ischemia was induced by clamping the left pulmonary hilum for 60 minutes. The drug (10 mg/kg) was administered intraperitoneally 30 minutes before ischemia. After 24 hours of reperfusion, lung tissues were harvested for histological analysis and measurement of oxidative stress markers [5]
Nude mice bearing GIST882 xenografts were treated with the drug orally at 40 mg/kg/day for 30 days. Survival time was recorded daily, and tumor tissues were analyzed for c-kit phosphorylation by Western blot [1]

Absorption, Distribution and Excretion
Imatinib is well absorbed after oral administration, reaching peak plasma concentration (Cmax) within 2–4 hours. The mean absolute bioavailability of the capsule formulation is 98%. In healthy volunteers, the elimination half-lives of its main active metabolite, the N-demethyl derivative, are approximately 18 hours and 40 hours, respectively. The mean AUC of imatinib increases proportionally with dose, ranging from 25 mg to 1000 mg. The pharmacokinetics of imatinib did not change significantly after repeated dosing; steady-state plasma accumulation was 1.5–2.5 times with once-daily administration of imatinib. At clinically relevant concentrations, in vitro studies showed that imatinib binds to approximately 95% of plasma proteins, primarily albumin and α1-acid glycoprotein. Fecal excretion: 68% of the drug was excreted within 7 days (20% of doses remained unchanged); Renal excretion: 13% of the drug was excreted within 7 days (5% of doses remained unchanged). Typically, imatinib clearance is expected to be 8 L/h in a 50-year-old patient weighing 50 kg, increasing to 14 L/h in a 50-year-old patient weighing 100 kg. However, a 40% difference in clearance between patients is not sufficient to adjust the initial dose based on weight and/or age, but suggests the need for close monitoring of treatment-related toxicities. In lactating female rats, administration of 100 mg/kg of imatinib and/or its metabolites resulted in significant excretion of the drug into breast milk. It is estimated that approximately 1% of the maternal dose is excreted into breast milk, which is equivalent to 30% of the maternal dose ingested per unit of infant body weight. Metabolism/Metabolites: CYP3A4 is the major enzyme responsible for the metabolism of imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play minor roles in its metabolism. The main circulating active metabolite in the human body is an N-demethylpiperazine derivative, primarily generated by CYP3A4. Its in vitro activity is similar to imatinib. The plasma AUC of this metabolite is approximately 15% of that of imatinib.
Biological Half-Life
Elimination - The elimination half-lives of imatinib and its main metabolite are approximately 18 hours and 40 hours, respectively.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that mothers taking up to 400 mg of imatinib daily have low concentrations of the drug and its active metabolites in breast milk. While a small number of breastfed infants appear to have experienced no adverse effects while their mothers were taking imatinib, long-term data are lacking. Close monitoring is recommended during breastfeeding with imatinib until more data become available. National Comprehensive Cancer Network (NCCN) guidelines, manufacturers, and some authors recommend discontinuing breastfeeding during imatinib treatment and for one month after treatment ends.
◉ Effects on Breastfed Infants
A woman with chronic myeloid leukemia (CML) took 400 mg of imatinib orally daily and was breastfeeding. The infant experienced no adverse effects during the first two months of breastfeeding.
A woman with CML continued taking imatinib 400 mg/day throughout pregnancy and lactation (breastfeeding duration not specified) until nearly 6 months postpartum. Her baby reportedly grew and developed normally. A woman with chronic myeloid leukemia (CML) started taking imatinib 400 mg/day from week 8 of pregnancy and continued until the end of breastfeeding (breastfeeding duration not specified). The baby was healthy but underwent atrial septal defect repair surgery at 30 months of age. This is believed to be unrelated to imatinib treatment. A pregnant woman with Philadelphia chromosome-positive CML started taking imatinib 400 mg/day during pregnancy. After delivery, her preterm infant was initially fed colostrum until mid-postpartum day 5, after which she was exclusively formula-fed. The infant received treatment for preterm apnea and was discharged on day 25. No adverse effects on growth and development were observed in the first year of life. ◉ Effects on breastfeeding and breast milk: As of the revision date, no relevant published information was found.

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Interaction
This study aimed to investigate the effects of co-administration of imatinib and idarubicin (an anthracycline with hemostatic activity) on nude mice and mouse bone marrow cells. Mice treated with the dual therapy group showed a significantly higher mortality rate compared to mice treated with imatinib or idarubicin alone, but this only occurred with co-administration of idarubicin and imatinib. Mice treated with the combination therapy group exhibited more severe neutropenia and slower recovery compared to mice treated with idarubicin alone. Myeloid metaplasia, typically observed in the spleen after idarubicin treatment, disappeared in mice co-treated with imatinib. The number of megakaryocytes and myeloid progenitor cells in the bone marrow of the dual-treated animals was also reduced. Imatinib inhibited SCF-induced proliferation and recovery after idarubicin treatment when mouse bone marrow cells were cultured in vitro. …These results indicate that co-administration of imatinib enhances the hematopoietic toxicity induced by idarubicin in vivo and in vitro.
Caution is advised when using Gleevec/imatinib with CYP3A4 family inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin). Substances that inhibit cytochrome P450 isoenzyme (CYP3A4) activity may reduce imatinib metabolism and increase its concentration.
Substances that induce CYP3A4 activity may increase imatinib metabolism and decrease its plasma concentration. Drugs used in combination with CYP3A4 inducers (e.g., dexamethasone, phenytoin sodium, carbamazepine, rifampin, phenobarbital, or St. John's wort) may reduce Gleevec (imatinib) exposure. …A patient taking phenytoin sodium long-term… taking 350 mg of Gleevec daily, had an AUC0-24 approximately one-fifth of the typical AUC0-24 (20 μg/h/mL). This may reflect the CYP3A4 induction effect of phenytoin sodium. Imatinib increased the mean Cmax and AUC of simvastatin (a CYP3A4 substrate) by 2-fold and 3.5-fold, respectively, suggesting that imatinib inhibits CYP3A4. Extra caution is advised when imatinib/gleevec is used in combination with CYP3A4 substrates with a narrow therapeutic window (e.g., cyclosporine or pimozide). Gleevec increases the plasma concentrations of other drugs metabolized by CYP3A4 (e.g., triazobenzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). For more complete data on interactions of imatinib mesylate (6 studies), please visit the HSDB records page. Mice treated with imatinib mesylate (STI571; Gleevec; Glivec) at a dose of 50 mg/kg/day for 28 days showed a slight decrease in body weight (approximately 6%), but no significant hepatotoxicity or nephrotoxicity was observed. Serum ALT, AST and creatinine levels were all within the normal range [4]
The plasma protein binding rate of the drug in human plasma was approximately 95% as determined by balanced dialysis [1]
In vitro cytotoxicity tests showed that the drug did not cause significant damage to normal human bronchial epithelial cells (BEAS-2B) at concentrations up to 5 μM [4]

[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.

Therapeutic Uses
Imatinib mesylate (Gleevec) is an inhibitor of abl, kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, reported to be effective in treating eosinophilia (HES) and a rare eosinophilic-associated chronic myeloid disease (eos-CMD) characterized by the t(5;12)(q33;p13) cytogenetic abnormality. In this study, we aimed to confirm preliminary observations in HES and evaluate the therapeutic value of imatinib in eos-CMD without t(5;12)(q33;p13). Five HES patients (all male, median age 46 years) and two eos-CMD patients (both male, ages 45 and 58 years, respectively) received imatinib at starting doses ranging from 100 to 400 mg/day. Cytogenetic studies showed no bcr-abl translocations or t(5;12)(q33;p13) translocations in any of the patients. Screening of exons encoding the intracellular catalytic domain and extracellular ligand-binding domain for PDGFRβ (exons 2-23) and c-kit (exons 1-21) in 6 patients revealed predominantly known genetic polymorphisms. With a median follow-up of 17 weeks (range 10-33 weeks), two HES patients and one eos-CMD patient achieved complete clinical remission, and one HES patient achieved partial remission. Contrary to previous observations, serum interleukin-5 levels were elevated in all four responding patients. A study included 28 patients with accelerated-phase chronic myeloid leukemia (CML)… The diagnosis of accelerated-phase CML was based on karyotype evolution (n = 9) and hematological criteria (n = 18). All patients received initial treatment with imatinib mesylate 600 mg/day. When the absolute neutrophil count (ANC) was <0.5/μL or the platelet count was <20,000/μL, the dose was gradually reduced to 400 mg/day, and finally to 300 mg/day. Of the 28 patients, 27 continued treatment, with a median treatment duration of 34 weeks. Thrombocytopenia developed in 11 patients after a mean treatment duration of 8.4 ± 1.4 weeks. The occurrence of thrombocytopenia was associated with disease progression in one patient and with megakaryocyte reduction in the bone marrow in another 10 patients. Platelet counts recovered to >20,000/μL in 9 patients after a mean of 19.7 ± 1.8 weeks. Patients who developed thrombocytopenia had a longer disease duration (9.39 years vs. 4.35 years; P < 0.01) and were more likely to be diagnosed with accelerated phase chronic myeloid leukemia (CML) according to hematological criteria. Hematological responses were similar in patients with and without thrombocytopenia; however, 31.3% of patients without thrombocytopenia achieved complete cytogenetic remission, while none of the patients with thrombocytopenia achieved complete cytogenetic remission. Grade III-IV thrombocytopenia is common in accelerated-phase chronic myeloid leukemia (CML) and may be a marker of failure to achieve cytogenetic remission with imatinib mesylate monotherapy. Imatinib is indicated for the treatment of gastrointestinal stromal tumors (GIST). /Not included in the US product label/ Imatinib is indicated for the treatment of patients with chronic-phase chronic myeloid leukemia (MCL) in blast crisis, accelerated phase, or after failure of interferon-alpha therapy. (Note: Efficacy is based on overall hematologic and cytogenetic remission rates. No controlled trials have yet confirmed clinical benefit, such as improvement of disease-related symptoms or prolongation of survival.) /US product label includes/
Imatinib mesylate (STI571, Gleevec) is a selective BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML). It represents how a deeper understanding of the pathogenesis of cancer can facilitate the development of targeted molecular therapies. Phase II clinical trials have shown that imatinib has significant therapeutic activity at all stages of CML development, especially in the chronic phase. In the chronic phase, imatinib achieved complete hematologic remission in almost 100% of patients who were resistant to or intolerant of interferon, with a major cytogenetic remission rate of 60%, including a complete cytogenetic remission rate of 41%. Preliminary results from the ongoing Phase II clinical trial show that imatinib has significant therapeutic activity at all stages of CML development. A phase III, multicenter, randomized study compared the efficacy of imatinib in combination with interferon and cytarabine as first-line treatment for chronic myeloid leukemia (CML). Results showed that imatinib was superior to other regimens in both efficacy and safety. If longer follow-up confirms these results, imatinib will become the preferred treatment for most CML patients, with allogeneic transplantation as initial treatment only suitable for young patients with a related donor.

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Drug Warning
Imatinib mesylate effectively blocks BCR/ABL kinase activity, making it a promising drug for treating Philadelphia chromosome-positive leukemia. Imatinib treatment has shown high hematologic and cytogenetic remission rates, but usually only mild non-hematologic side effects such as rash, edema, and muscle spasms occur. …Two cases of acute generalized pustular eczema induced by imatinib have been reported. Both patients developed generalized pustular eczema after 12 weeks of treatment. After initiating imatinib treatment, multiple microbiological examinations were performed to rule out infectious causes. Histopathological examination of the skin lesions was consistent with acute generalized pustular eczema. ...The skin recovered completely after discontinuation of imatinib. ...Tyrosine kinase inhibitors (STI571, Gleevec) have recently been used to treat chronic myeloid leukemia. ...This article details a case of pityriasis rosea developed while taking Gleevec in a patient experiencing the blast crisis of chronic myeloid leukemia. ...Imatinib or STI 571...belongs to a new class of drugs called signal transduction inhibitors. These compounds specifically inhibit the proliferation of cells expressing v-abl and bcr-abl and have recently been approved for the treatment of chronic myeloid leukemia (CML). ...Erosive oral lichen planus-like lesions. This article reports a case of a 72-year-old female patient with chronic myeloid leukemia (CML) who developed a rash limited to the buccal mucosa and dorsum of the tongue 12 weeks after starting imatinib. Histological examination was consistent with lichen planus-like drug eruption. Skin lesions subsided after discontinuation of the drug. Adverse reactions with an incidence ≥10% include nausea, vomiting, edema, muscle cramps, diarrhea, gastrointestinal or central nervous system bleeding, musculoskeletal pain, rash, headache, fatigue, arthralgia, indigestion, myalgia, weight gain, fever, abdominal pain, cough, dyspnea, anorexia, constipation, nasopharyngitis, night sweats, pruritus, epistaxis, hypokalemia, petechiae, pneumonia, and asthenia. For more imatinib drug warnings (full version), please refer to imatinib mesylate (11 cases in total), please visit the HSDB record page. Imatinib mesylate (STI571; Gleevec; Glivec) is a selective oral tyrosine kinase inhibitor that targets c-kit, ABL, and PDGFRβ, blocking downstream signaling pathways involved in cell proliferation, survival, and invasion [1,3]. It is the first FDA-approved targeted therapy for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST) with c-kit or BCR-ABL mutations[1]. In addition to its anticancer activity, the drug also has a protective effect against ischemia/reperfusion injury by reducing oxidative stress and inflammation[5]. It can synergize with other drugs (such as vitamin D analogs) to enhance antitumor efficacy, providing a potential strategy for combination therapy of solid tumors[4].

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.)