| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
Inhibitor of multiple kinases including VEGFRs, PDGFRs, c-KIT, and Raf kinases. [1]
It is classified as a type IIA inhibitor, binding to the DFG-out, αC-helix-in inactive conformation of kinases. [1] |
|---|---|
| ln Vitro |
B-Raf inhibitor 1 (compound 13) has an IC50 of 0.31 μM and suppresses the proliferation of A375 and HCT-116, respectively. Compound 13—B-Raf inhibitor 1—binds to B-Raf and stabilizes it in the DFG-out, inactive conformation, where Phe595 and Gly596 in the DFG motif partially fill the ATP pocket. Low micromolar inhibition of wild-type B-Raf cell lines was also seen with B-Raf inhibitor 1 (compound 13), which may have been caused by pan-Raf inhibition (including Raf dimers) or off-target kinase activity [1].
Sorafenib is a type IIA Raf kinase inhibitor with an IC50 of 22 nM against wild-type B-Raf and 38 nM against C-Raf. [1] It exhibits a broad kinase selectivity profile, with significant activity against other kinases including RET, KIT, VEGFRs, PDGFRs, and TIE1. Its selectivity score (S at 1 μM) is 0.14 against a panel of 314 kinases, indicating it is not a highly selective B-Raf inhibitor. [1] In cellular assays, sorafenib inhibits the proliferation of A375 (B-RafV600E) cells with an IC50 of 2.4 μM. [1] It inhibits the proliferation of Colo205 and A549 cell lines with IC50 values in the 2-4 μM range. [1] The effect of sorafenib on MAPK pathway activation in wild-type B-Raf cells is mixed. One study reported no MAPK activation in cells treated with 10 μM of the compound, while another found that lower concentrations could activate the pathway. [1] Sorafenib can induce Raf dimerization. [1] |
| ln Vivo |
Sorafenib demonstrates in vivo tumor growth inhibition in various xenograft models, including Colo205 and A549. [1]
Cutaneous squamous cell carcinoma is an observed side effect in patients taking sorafenib. [1] |
| Enzyme Assay |
The review summarizes enzyme activity data from primary literature. Sorafenib's inhibitory activity against various kinases (IC50 or Ki values) was determined in biochemical assays using purified kinase domains, likely with radioactive or mobility shift assays at specific ATP concentrations (e.g., 100 μM for some measurements). [1]
|
| Cell Assay |
The review summarizes cell assay data from primary literature. Cell proliferation IC50 values for sorafenib were determined in cell lines such as A375 (B-RafV600E mutant), Colo205, and A549, likely using standard viability assays (e.g., MTT, CellTiter-Glo) after a defined period of compound treatment. [1]
The effect on MAPK pathway activation was assessed by measuring phosphorylated ERK (p-ERK) levels via Western blot or immunoassay in cells treated with varying concentrations of sorafenib. [1] |
| Animal Protocol |
The review mentions in vivo efficacy studies where sorafenib was administered to mice bearing tumor xenografts (e.g., Colo205, A549). Specific details on formulation, dose, route (likely oral), and schedule are not provided in this review but are referenced from the primary literature. [1]
The review mentions in vivo efficacy studies where sorafenib was administered to mice bearing tumor xenografts (e.g., Colo205, A549). Specific details on formulation, dose, route (likely oral), and schedule are not provided in this review but are referenced from the primary literature. [1] |
| Toxicity/Toxicokinetics |
Cutaneous squamous cell carcinoma is reported as a clinical side effect in patients treated with sorafenib. [1]
In preclinical studies, a potent and selective type IIA inhibitor (compound 13) was reported to cause hyperplasia in a mouse model, suggesting that this class of inhibitors, including sorafenib, may have proliferative effects in normal tissues. [1] |
| References | |
| Additional Infomation |
Sorafenib is an approved kinase inhibitor drug used as an antiangiogenesis agent for the treatment of renal cell carcinoma. [1]
It is classified as a type IIA inhibitor because it binds to and stabilizes the inactive DFG-out conformation of its target kinases. [1] Unlike selective type I and type IIB B-Raf inhibitors, sorafenib exhibits broad kinase inhibition, including significant activity against receptor tyrosine kinases. This off-target activity may contribute to its effects on wild-type B-Raf cell lines. [1] Its ability to activate the MAPK pathway in wild-type B-Raf cells is thought to be linked to the induction of Raf dimerization. The clinical observation of cutaneous squamous cell carcinoma in patients taking sorafenib is likely a consequence of this pathway activation. [1] |
| Molecular Formula |
C26H19N8CL.2[HCL]
|
|---|---|
| Molecular Weight |
551.85754
|
| Exact Mass |
550.095
|
| CAS # |
1191385-19-9
|
| Related CAS # |
Raf inhibitor 1;1093100-40-3
|
| PubChem CID |
44247765
|
| Appearance |
Light yellow to yellow solid
|
| LogP |
8.162
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
37
|
| Complexity |
690
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC=C2C(C=CN=C2NC3=CC=C(Cl)C=C3)=C1NC4=NC=CC=C4C5=NC=NC6=C5N=CN6.[H]Cl.[H]Cl
|
| InChi Key |
HRLQRNBAJCQMMG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H19ClN8.2ClH/c1-15-4-9-19-18(10-12-29-24(19)34-17-7-5-16(27)6-8-17)21(15)35-25-20(3-2-11-28-25)22-23-26(32-13-30-22)33-14-31-23;;/h2-14H,1H3,(H,28,35)(H,29,34)(H,30,31,32,33);2*1H
|
| Chemical Name |
1-N-(4-chlorophenyl)-6-methyl-5-N-[3-(7H-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine;dihydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
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. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~10 mg/mL (~18.1 mM; with ultrasonication and warming by heating to 60°C)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (1.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (10.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 mg/mL (1.81 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 DMSO stock solution (10.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 1 mg/mL (1.81 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 DMSO stock solution (10.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8121 mL | 9.0603 mL | 18.1205 mL | |
| 5 mM | 0.3624 mL | 1.8121 mL | 3.6241 mL | |
| 10 mM | 0.1812 mL | 0.9060 mL | 1.8121 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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