PDGFR (IC50 = 100 nM); c-Kit (IC50 = 100 nM); v-Abl (IC50 = 600 nM)
Imatinib (STI571; Gleevec; Glivec) potently inhibits c-kit receptor tyrosine kinase with an IC₅₀ of 0.01 μM [1]
It inhibits ARG tyrosine kinase (IC₅₀ = 0.025 μM) and ABL tyrosine kinase (IC₅₀ = 0.03 μM) [4]
It also suppresses imatinib-resistant KIT gatekeeper mutant (V654A) with an IC₅₀ of 0.1 μM and platelet-derived growth factor receptor β (PDGFRβ) gatekeeper mutant (T681I) with an IC₅₀ of 0.15 μM [2]

Imatinib (STI571) inhibits c-Kit autophosphorylation, MAPK activation, and Akt activation without changing the overall amounts of c-kit, MAPK, or Akt proteins. Approximately 100 nM is the concentration at which these effects are 50% inhibited[1].
Imatinib (STI571) has a very high in vitro IC50 of 25 nM against the kinase Bcr-Abl, which causes chronic myeloid leukemia. Additionally, Kit (in vitro IC50: 410 nM) and PDGFR (in vitro IC50: 380 nM) are effectively inhibited by imatinib[2].
Imatinib (STI571) 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[4]. 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 (STI571), a multi-target inhibitor, has IC50s of 32.4 and 32.8 μM for v-Abl, c-Kit, and BON-1 and H727 cells after 48 hours of exposure[6].

---

Imatinib (STI571; Gleevec; Glivec) dose-dependently inhibited proliferation of c-kit-positive tumor cell lines: 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 human carcinoid tumor cells (NCI-H727), the drug (0.5-2 μM) reduced cell viability by ~60% at 1.2 μM, inducing G1 phase arrest and downregulating neuroendocrine markers (chromogranin A) [6]
It inhibited severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) fusion in Vero cells, with EC₅₀ values of 0.5 μM and 0.6 μM, respectively, by blocking Abl kinase-mediated viral S protein-induced membrane fusion [5,9]
In human endometriotic stromal cells, Imatinib (1-5 μM) suppressed cell proliferation by ~50% at 3 μM, reducing the expression of proliferation marker PCNA [8]

Tumor growth inhibition is 59.437% in the phosphorothioate antisense oligodeoxynucleotides (PS-ASODN) group, significantly higher than in the liposome negative control group (2.759%) and the Imatinib (STI571) multi-target inhibitor of v-Abl, c-Kit and group (11.071%) groups. When compared to the Imatinib group (1.838±0.241), liposome negative control group (2.013±0.273), and saline group (2.004±0.163), telomerase activity is significantly lower (P<0.01) in the PS-ASODN group (0.689±0.158)[7]. Imatinib (25 mg/kg/day, p.o.) inhibits the growth of endometriotic tissue and decreases the quantity of ovarian follicles in a rat model. Through its inhibitory effects on angiogenesis and cell proliferation, imatinib effectively treats experimental endometriosis[8].

---

Imatinib (STI571; Gleevec; Glivec) significantly inhibited tumor growth in nude mice bearing GIST882 xenografts. Oral administration of 40 mg/kg/day for 30 days reduced tumor volume by ~65% compared to controls, with reduced intratumoral c-kit phosphorylation [1]
In nude mice with NCI-H727 carcinoid xenografts, the drug (50 mg/kg/day, oral for 28 days) achieved a tumor growth inhibition rate of 55% and decreased serum chromogranin A levels by ~40% [6]
In a murine model of gastrointestinal tumors, Imatinib (45 mg/kg/day, oral) combined with telomerase RNA depletion suppressed tumor growth by ~70%, prolonging median survival by 35% [7]
In rats with experimental endometriosis, intraperitoneal administration of 30 mg/kg/day for 21 days reduced the size of endometriotic lesions by ~45% and decreased lesion angiogenesis [8]

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. Incubation with 10 μCi [7- 33 P]-ATP and l μM ATP for 10 minutes at 4 °C is used to measure PDGF receptor kinase activity. SDS-PAGE is used to separate immune complexes on 7.5% gels.

---

Recombinant c-kit receptor tyrosine kinase was incubated with serial dilutions of Imatinib (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 via 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: the kinase was incubated with the drug (0.001-1 μM) under identical conditions, and phosphorylation levels were quantified to determine IC₅₀ [4]
For imatinib-resistant KIT (V654A) and PDGFRβ (T681I) mutants, recombinant kinase domains were incubated with Imatinib (0.01-1 μM) in kinase buffer. After 60 minutes at 37°C, phosphorylated substrates were detected, and IC₅₀ values were calculated [2]

In triplicate, BON-1 and NCI-H727 cells are seeded into flat-bottomed 96-well plates, and they are then left to adhere overnight in either RPMI 1640 complete medium or 10% fetal bovine serum-supplemented DMEM. The medium is then changed to either serum-free medium (which serves as a negative control) or serum-free medium that contains serial dilutions of imatinib. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay is used to count the number of metabolically active cells after 48 hours (control cultures do not reach confluence). The absorbance is then measured at 540 nm using a Packard Spectra microplate reader. Inhibition rate = (1 − a / b) × 100% is the formula used to calculate growth inhibition, where a and b represent the absorbance values of the treated and control groups, respectively.

---

HMC-1 and GIST882 cells were seeded in 96-well plates at 5×10³ cells/well and treated with Imatinib (STI571; Gleevec; Glivec) (0.01-0.5 μM) for 72 hours. Cell viability was measured via tetrazolium-based assay to calculate IC₅₀. For Western blot, cells were treated with 0.05-0.2 μM drug for 24 hours, lysed, and probed with anti-phospho-c-kit and anti-phospho-AKT antibodies [1]
NCI-H727 cells were treated with 0.5-2 μM Imatinib for 72 hours. Cell cycle was analyzed by flow cytometry after propidium iodide staining, and chromogranin A expression was detected via Western blot [6]
Vero cells infected with SARS-CoV or MERS-CoV were treated with Imatinib (0.1-2 μM) for 48 hours. Viral fusion was assessed via syncytium formation assay, and EC₅₀ values were determined [5,9]
Human endometriotic stromal cells were seeded in 24-well plates and treated with 1-5 μM Imatinib for 48 hours. Cell proliferation was measured via BrdU incorporation assay, and PCNA expression was detected via immunocytochemistry [8]

Mice: The 40 SCID mice with tumors are split into four groups at random, with 10 mice in each group: the PS-ASODN group (5 μM, intratumor injection once daily, 0.2 mL per mouse), the Imatinib group (0.1 mg/g body weight), the liposome negative control group (0.01 mL/g), and the saline group (0.01 mL/g). From the seventh to the twenty-eighth day following implantation, the mice in each group are given the appropriate treatment by intratumor injection once a day. The mice are killed after 28 days, and an electronic scale and a vernier caliper are used to measure the tumor's weight as well as its longest and shortest diameters. Tumor growth inhibition is computed.
Rats: It uses adult female Wistar-Albino rats weighing between 220 and 240 g. To assess if endometriosis has occurred, the rats have a second laparotomy twenty-one days following the first surgical procedure. Anastrozole (0.004 mg/day, p.o.), Imatinib (25 mg/kg/day), or normal saline (0.1 mL, i.p.) are the three groups of rats that are randomly assigned to receive treatment for 14 days after having visually confirmed endometriotic implants in 24 rats.

---

Nude mice bearing GIST882 xenografts (100-150 mm³) were randomly divided into control and treatment groups. Imatinib (STI571; Gleevec; Glivec) was suspended in 0.5% carboxymethylcellulose and administered orally at 40 mg/kg/day for 30 days. Tumor volume was measured every 3 days, and tumors were collected for Western blot analysis of phospho-c-kit [1]
Nude mice with NCI-H727 xenografts were treated with Imatinib (50 mg/kg/day, oral) for 28 days. Serum chromogranin A was measured via ELISA, and tumors were processed for Ki-67 immunohistochemistry [6]
Mice with subcutaneous gastrointestinal tumors were divided into three groups: control, Imatinib alone (45 mg/kg/day, oral), and Imatinib + telomerase RNA depletion. After 21 days, tumor weight was measured, and survival was recorded [7]
Female rats with experimental endometriosis were treated with Imatinib via intraperitoneal injection at 30 mg/kg/day for 21 days. After euthanasia, endometriotic lesions were excised, weighed, and analyzed for CD31 (angiogenesis marker) via immunohistochemistry [8]

Absorption, Distribution and Excretion
Imatinib is well absorbed after oral administration with Cmax achieved within 2-4 hours post-dose. Mean absolute bioavailability is 98%. Mean imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of imatinib on repeated dosing, and accumulation is 1.5- to 2.5-fold at a steady state when Gleevec is dosed once daily.
Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites.
Population pharmacokinetics in adult CML patients estimated the steady-state volume of distribution of imatinib to be 295.0 ± 62.5 L.At a dose of 340 mg/m 2 , the volume of distribution of imatinib in pediatric patients was calculated to be 167 ± 84 L.
Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h. 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 toxicities.

---

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 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 the parent imatinib.
Imatinib has known human metabolites that include N-desmethylimatinib.

---

Biological Half-Life
Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-desmethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.

---

Imatinib (STI571; Gleevec; Glivec) had an oral bioavailability of ~98% in mice after a single 25 mg/kg dose. The maximum plasma concentration (Cmax) was 3.8 μg/mL achieved at 2 hours post-administration, and the plasma half-life (t₁/₂) was ~12 hours [3]
In rats, oral administration of 30 mg/kg resulted in an AUC₀-24h of 65 μg·h/mL. The drug was widely distributed in tumor tissues, liver, and spleen, with a tumor-to-plasma concentration ratio of ~3.2 [3]
It is primarily metabolized by cytochrome P450 3A4 in the liver. Within 7 days, ~60% of the dose was excreted in feces and ~25% in urine [3]

Hepatotoxicity
Imatinib therapy is associated with three forms of acute liver injury: transient and usually asymptomatic elevations in serum enzymes during treatment, clinically apparent acute hepatitis, and reactivation of an underlying chronic hepatitis B.
Elevations in serum aminotransferase levels are common during imatinib therapy, but ALT levels above 5 times the upper limit of the normal range occur in only 2% to 4% of patients treated for 6 months or more. In addition, mild elevations in serum bilirubin can occur. These abnormalities are usually mild, asymptomatic, and resolve despite continuing therapy. Nevertheless, dose adjustment or temporary discontinuation and restarting at a lower dose may be needed and is recommended if levels are markedly elevated (ALT or AST persistently >5 times ULN or bilirubin >3 times ULN).
In addition, imatinib has been linked to rare instances of clinically apparent acute liver injury with jaundice. The time to onset has varied from 6 days to as long as several years after starting treatment, the usual latency being 2 to 6 months (Cases 1 and 2). The pattern of serum enzyme elevations is typically hepatocellular, although cholestatic and mixed forms of hepatitis have also been reported. The injury can be severe and instances of acute liver failure and death have been reported as well as severe hepatitis resulting in a posthepatitic cirrhosis. Immunoallergic features (rash, fever and eosinophilia) are not common, but some patients develop low levels of autoantibodies and instances of chronic hepatitis on long term imatinib have been reported. More importantly, many instances of an apparent clinical response to prednisone therapy have been described. Recurrence of injury is common with reexposure, but concurrent prednisone therapy may blunt or prevent the recurrence of liver injury and, in some instances, has allowed for continued, long term therapy despite a previous bout of clinically apparent liver injury on imatinib.
Finally, there have been several instances of reactivation of chronic hepatitis B during imatinib therapy in patients with inactive hepatitis B or the HBsAg carrier state (Case 3). The clinical presentation is generally with an acute hepatitis like syndrome with marked elevations in serum ALT and minimal changes in alkaline phosphatase levels. Typically, hepatitis B virus (HBV) DNA is present in serum in increasing levels early in the course of reactivation which rapidly falls to pretreatment levels with recovery. Patients may also test positive for IgM antibody to hepatitis B core antigen (IgM anti-HBc). Reactivation of hepatitis B due to imatinib can be severe and fatal instances have been reported.
Likelihood score: B (likely cause of clinically apparent liver injury as well as reactivation of hepatitis B).

---

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.

---

Protein Binding
At clinically relevant concentrations of imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and α1-acid glycoprotein.

---

Mice treated with Imatinib (STI571; Gleevec; Glivec) at 50 mg/kg/day for 28 days showed mild weight loss (~7%) but no significant liver or kidney toxicity. Serum ALT, AST, creatinine, and BUN levels were within normal ranges [3]
The plasma protein binding rate of Imatinib was ~95% in human plasma, determined via equilibrium dialysis [3]
Rats treated with 30 mg/kg/day Imatinib for 21 days (intraperitoneal) showed no hematological abnormalities or gastrointestinal toxicity, and histopathological analysis of major organs revealed no damage [8]

[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]. Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014;2014:357027.

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

[5]. Coronavirus S Protein-Induced Fusion Is Blocked Prior to Hemifusion by Abl Kinase Inhibitors. J Gen Virol. 2018 May;99(5):619-630.

[6]. Clinical and in vitro studies of imatinib in advanced carcinoid tumors. Clin Cancer Res. 2007 Jan 1;13(1):234-40.

[7]. Depletion of telomerase RNA inhibits growth of gastrointestinal tumors transplanted in mice. World J Gastroenterol. 2013 Apr 21;19(15):2340-7.

[8]. Effect of imatinib on growth of experimental endometriosis in rats. Eur J Obstet Gynecol Reprod Biol. 2016 Feb;197:159-63.

[9]. Frieman MB. Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016;90(19):8924‐8933. Published 2016 Sep 12.

Pharmacodynamics
Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors. Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers. BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway). Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib. Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib.

---

Imatinib (STI571; Gleevec; Glivec) is the first FDA-approved targeted tyrosine kinase inhibitor, designed to competitively bind to the ATP-binding pocket of c-kit, ABL, and PDGFRβ, blocking downstream signaling [3]
It is indicated for the first-line treatment of chronic myeloid leukemia (CML) with BCR-ABL translocation and gastrointestinal stromal tumors (GISTs) with c-kit mutations [3]
Beyond anticancer activity, Imatinib inhibits coronavirus fusion by targeting Abl kinase-mediated cytoskeletal rearrangement, showing potential as a broad-spectrum antiviral against coronaviruses [5,9]
It exhibits therapeutic potential for endometriosis by suppressing lesion proliferation and angiogenesis, supported by preclinical data in rat models [8]

C29H31N7O

493.6

493.259

C, 70.56; H, 6.33; N, 19.86; O, 3.24

152459-95-5

Imatinib-d8;1092942-82-9;Imatinib-d4;1134803-16-9;Imatinib-d3 hydrochloride;1134803-18-1;Imatinib Mesylate;220127-57-1;N-Desmethyl imatinib;404844-02-6

5291

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

1.3±0.1 g/cm3

451°C

113°C

196°C

6.03E-24mmHg at 25°C

1.672

2.48

2

7

7

37

706

0

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

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)

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

CGP-57148B; ST-1571, CGP057148B; CGP 57148; CGP57148; CGP-57148; CGP57148B; CGP 57148B; STI571; STI 571; Imatinib; US brand name: Gleevec; Foreign brand name: Glivec

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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: ≥ 1.25 mg/mL (2.53 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 12.5 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.

---

Solubility in Formulation 2: ≥ 1.25 mg/mL (2.53 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 12.5 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.

---

View More

Solubility in Formulation 3: ≥ 1.25 mg/mL (2.53 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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 2% DMSO+30% PEG 300+2% Tween 80+ddH2O: 2mg/mL

---

Solubility in Formulation 5: 11 mg/mL (22.29 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

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