TP-0903
Description:
IC50: 0.027 μM against AXL
AXL and other TAM family members are known to be involved in maintaining the mesenchymal phenotype in cancer cells. Mesenchymal cells have increased invasion and migratory properties, enhanced cell survival in stressed environments, as well as increased resistance to targeted therapies. TP-0903 is a potent anti-cancer agent targeting the AXL receptor tyrosine kinase.
In vitro: On the basis of the potency of TP-0903 in biochemical assays, its activity in cell-based studies was evaluated. TP-0903 showed extremely potent activity in cell viability assays against the pancreatic cancer cell line PSN-1. More importantly, TP-0903 was evaluated for its ability to block GAS6-mediated activation of AXL in pancreatic cancer cells. PSN-1 cells were serum-starved and then stimulated with GAS6 in the presence of various concentrations of TP-0903 [1].
In vivo: TP-0903 restores sensitivity to erlotinib in cell-based and preclinical animal models of cancer by reversing the mesenchymal phenotype driving resistance [2].
Clinical trial: Up to now, TP-0903 is still in the preclinical development stage.
Reference:
[1] Mollard A, Warner SL, Call LT, Wade ML, Bearss JJ, Verma A, Sharma S, Vankayalapati H, Bearss DJ. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Med Chem Lett. 2011 Dec 8;2(12):907-912.
[2] ToleroPharmaceuticals, Inc–TP-0903. http://www.toleropharmaceuticals.com/TP-0903.html.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 516.06 |
| Cas No. | 1341200-45-0 |
| Formula | C24H30ClN7O2S |
| Solubility | ≥25.8 mg/mL in DMSO with gentle warming; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 2-((5-chloro-2-((4-((4-methylpiperazin-1-yl)methyl)phenyl)amino)pyrimidin-4-yl)amino)-N,N-dimethylbenzenesulfonamide |
| SDF | Download SDF |
| Canonical SMILES | CN(S(C1=CC=CC=C1NC2=NC(NC3=CC=C(CN4CCN(CC4)C)C=C3)=NC=C2Cl)(=O)=O)C |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment:[1] | |
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Cell lines |
Pancreatic cancer cell line PSN-1 |
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Reaction Conditions |
6 nM TP-0903 (IC50) |
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Applications |
TP-0903 showed extremely potent activity in cell viability assays with an IC50 of 6 nM against PSN-1 cells. When PSN-1 cells was stimulated by GAS6, TP-0903 was able to dose-dependently decrease phospho-AKT and phospho-AXL levels with an EC50 of 305 and 222 nM, respectively. |
| Animal experiment:[2] | |
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Animal models |
An HCT116 mouse xenograft model and a KRAS-mutant colorectal cancer (CRC) patient-derived xenograft (PDX) mouse model |
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Dosage form |
40 mg/kg Administered orally |
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Applications |
TP-0903 exhibited 69 and 44% tumor growth inhibition in an HCT116 mouse xenograft model and a KRAS-mutant PDX mouse model, respectively, when administered at a dose of 40 mg/kg. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Mollard A, Warner SL, Call LT, et al. Design, Synthesis and Biological Evaluation of a Series of Novel Axl Kinase Inhibitors. ACS Medicinal Chemistry Letters, 2011, 2(12): 907-912. 2. Mangelson R, Peterson P, Foulks JM, et al. Abstract 2197: The AXL kinase inhibitor, TP-0903, demonstrates efficacy in preclinical models of colorectal cancer independent of KRAS mutation status. Cancer Research, 2019, 79(13 Suppl): Abstract nr 2197. |
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Quality Control & MSDS
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Chemical structure
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