WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206616
CAS#: 1365267-27-1 (X376)
Description: X-376 is an ALK inhibitor and potentially useful in non-small cell lung cancer. Caution: Many vendora are mistakenly selling X-376 as Ensartinib (X396, X-396, X 396). The structure is slightly different (see Cat#206013)
MedKoo Cat#: 206616
Name: X-376
CAS#: 1365267-27-1 (X376)
Chemical Formula: C25H25Cl2FN6O3
Exact Mass: 546.1349
Molecular Weight: 547.4124
Elemental Analysis: C, 54.85; H, 4.60; Cl, 12.95; F, 3.47; N, 15.35; O, 8.77
Related CAS #: 1370651-20-9 (X396) 1365267-27-1 (X376)
Synonym: X-376; X 376; X376; Ensartinib-analog; X 396-analog; X396-analog; X-396-analog;
IUPAC/Chemical Name: 6-Amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(4-methyl-1-piperazinyl)carbonyl]phenyl]-3-pyridazinecarboxamide
InChi Key: ONPGOSVDVDPBCY-CQSZACIVSA-N
InChi Code: InChI=1S/C25H25Cl2FN6O3/c1-14(21-17(26)7-8-18(28)22(21)27)37-20-13-19(31-32-23(20)29)24(35)30-16-5-3-15(4-6-16)25(36)34-11-9-33(2)10-12-34/h3-8,13-14H,9-12H2,1-2H3,(H2,29,32)(H,30,35)/t14-/m1/s1
SMILES Code: O=C(C1=NN=C(N)C(O[C@@H](C2=C(Cl)C=CC(F)=C2Cl)C)=C1)NC3=CC=C(C(N4CCN(C)CC4)=O)C=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | X-376 is an ALK tyrosine kinase inhibitor with an IC50 of 0.61 nM. |
| In vitro activity: | To compare the in vitro effects of X-376 versus PF-1066, the ability of both agents to inhibit the growth of four different cancer cell lines known to harbor ALK fusions or point mutations was tested. In H3122 lung cancer cells harboring EML4-ALK E13;A20 (variant 1), X-376 was 3-fold more potent than PF-1066 (IC50: PF-1066 180nM, X-376 77nM) (Fig. 2A and Table 2). Similar results were obtained with H2228 lung cancer cells (Fig. 2B), SUDHL-1 lymphoma cells (Fig. 2C), and SY5Y neuroblastoma cells (Fig. 2D), which harbor an EML4-ALK E6a/b;A20 (variant 3a/b) fusion, an NPM-ALK fusion, and an activating point mutation within the ALK kinase domain (F1174L) (12), respectively. In H3122 cells, the relative decrease in cell growth seen with X-376 treatment correlated with increased apoptosis, as assessed by fluorescence-activated cell sorting for Annexin V and propidium iodide (Fig. 2E). Reference: Cancer Res. 2011 Jul 15;71(14):4920-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138877/ |
| In vivo activity: | Nude mice harboring H3122 xenografts were treated with either X-376 at 50mg/kg bid. X-376 significantly delayed the growth of tumors compared to vehicle (Fig. 3A). At the dose used in these xenograft experiments, plasma levels inversely correlated with cellular potency. X-376 appeared well-tolerated in vivo. Mouse weight was unaffected by the treatment (Fig. 3B). Reference: Cancer Res. 2011 Jul 15;71(14):4920-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138877/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Ethanol | 13.0 | 23.75 |
The following data is based on the product molecular weight 547.4124 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25. PMID: 21613408; PMCID: PMC3138877. |
| In vitro protocol: | 1. Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25. PMID: 21613408; PMCID: PMC3138877. |
| In vivo protocol: | 1. Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25. PMID: 21613408; PMCID: PMC3138877. |
1: Sullivan I, Planchard D. ALK inhibitors in non-small cell lung cancer: the latest evidence and developments. Ther Adv Med Oncol. 2016 Jan;8(1):32-47. doi: 10.1177/1758834015617355. Review. PubMed PMID: 26753004; PubMed Central PMCID: PMC4699265.
2: Qiu W, Yuchi M, Ding M, Tessier D, Fenster A. Needle segmentation using 3D Hough transform in 3D TRUS guided prostate transperineal therapy. Med Phys. 2013 Apr;40(4):042902. doi: 10.1118/1.4795337. PubMed PMID: 23556924.
3: Lovly CM, Heuckmann JM, de Stanchina E, Chen H, Thomas RK, Liang C, Pao W. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31. doi: 10.1158/0008-5472.CAN-10-3879. Epub 2011 May 25. PubMed PMID: 21613408; PubMed Central PMCID: PMC3138877.
4: Byrne PV. Human myeloid cells possessing high-affinity receptors for granulocyte-macrophage colony stimulating factor. Leuk Res. 1989;13(2):117-26. PubMed PMID: 2538682.
