WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 206798
CAS#: 1956366-10-1 (HCl)
Description: Ulixertinib, also known as BVD-523 and VRT752271, is an inhibitors of ERK protein kinase. Downmodulation of ERK protein kinase activity inhibits VEGF secretion by human myeloma cells and myeloma-induced angiogenesis. Upon oral administration, BVD-523 inhibits both ERK 1 and 2, thereby preventing the activation of ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
MedKoo Cat#: 206798
Name: Ulixertinib HCl
CAS#: 1956366-10-1 (HCl)
Chemical Formula: C21H23Cl3N4O2
Exact Mass:
Molecular Weight: 469.791
Elemental Analysis: C, 53.69; H, 4.93; Cl, 22.64; N, 11.93; O, 6.81
Related CAS #: 1956366-10-1 (HCl) 869886-67-9 (free base) 1975172-95-2 (HCl hydrate)
Synonym: BVD-523, BVD 523, BVD523, VRT752271, VRT752271, VRT 752271, Ulixertinib hydrochloride
IUPAC/Chemical Name: (S)-4-(5-chloro-2-(isopropylamino)pyridin-4-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide hydrochloride.
InChi Key: DKGYQCPFBWFTHM-FSRHSHDFSA-N
InChi Code: InChI=1S/C21H22Cl2N4O2.ClH/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13;/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29);1H/t19-;/m1./s1
SMILES Code: O=C(C1=CC(C2=CC(NC(C)C)=NC=C2Cl)=CN1)N[C@@H](C3=CC=CC(Cl)=C3)CO.[H]Cl
Appearance: White to off-white 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: | Ulixertinib (BVD-523; VRT752271) is an inhibitor of ERK1/2 kinases with an IC50 of <0.3 nM against ERK2. |
| In vitro activity: | Whether ulixertinib could antagonize multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters was investigated. The results showed that ulixertinib, at non-toxic concentrations, significantly reversed ATP-binding cassette subfamily B member 1 (ABCB1)- and ATP-binding cassette subfamily G member 2 (ABCG2)-mediated MDR. In ABCB1-overexpressing cells, ulixertinib antagonized MDR by attenuating the efflux function of ABCB1. Similarly, in ABCG2-overexpressing cells, ulixertinib inhibited the efflux activity of ABCG2 and reversed resistance to substrate anticancer drugs. The reversal effects of ulixertinib were not related to the down-regulation or change of subcellular localization of ABCB1 or ABCG2. Mechanistic investigations revealed that ulixertinib stimulated the ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner, and the in silico docking study predicted that ulixertinib could interact with the substrate-binding sites of both ABCB1 and ABCG2. Reference: Biochem Pharmacol. 2018 Dec;158:274-285. https://www.sciencedirect.com/science/article/abs/pii/S0006295218304556?via%3Dihub |
| In vivo activity: | In in vivo xenograft studies, BVD-523 showed dose-dependent growth inhibition and tumor regression. BVD-523 yielded synergistic antiproliferative effects in a BRAFV600E-mutant melanoma cell line xenograft model when used in combination with BRAF inhibition. Antitumor activity was also demonstrated in in vitro and in vivo models of acquired resistance to single-agent and combination BRAF/MEK-targeted therapy. Reference: Mol Cancer Ther. 2017 Nov;16(11):2351-2363. https://mct.aacrjournals.org/content/16/11/2351.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 65.0 | 138.36 | |
| DMSO:PBS (pH 7.2) (1:3) | 0.25 | 0.53 | |
| DMF | 30.0 | 63.86 | |
| Ethanol | 1.0 | 2.13 |
The following data is based on the product molecular weight 469.791 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. Ji N, Yang Y, Lei ZN, Cai CY, Wang JQ, Gupta P, Xian X, Yang DH, Kong D, Chen ZS. Ulixertinib (BVD-523) antagonizes ABCB1- and ABCG2-mediated chemotherapeutic drug resistance. Biochem Pharmacol. 2018 Dec;158:274-285. doi: 10.1016/j.bcp.2018.10.028. Epub 2018 Oct 26. PMID: 30431011. 2. Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. PMID: 28939558. |
| In vitro protocol: | 1. Ji N, Yang Y, Lei ZN, Cai CY, Wang JQ, Gupta P, Xian X, Yang DH, Kong D, Chen ZS. Ulixertinib (BVD-523) antagonizes ABCB1- and ABCG2-mediated chemotherapeutic drug resistance. Biochem Pharmacol. 2018 Dec;158:274-285. doi: 10.1016/j.bcp.2018.10.028. Epub 2018 Oct 26. PMID: 30431011. |
| In vivo protocol: | 1. Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. PMID: 28939558. |
1: Kumar R, Suresh PS, Rudresh G, Zainuddin M, Dewang P, Kethiri RR, Rajagopal S, Mullangi R. Determination of ulixertinib in mice plasma by LC-MS/MS and its application to a pharmacokinetic study in mice. J Pharm Biomed Anal. 2016 Jun 5;125:140-4. doi: 10.1016/j.jpba.2016.03.036. PubMed PMID: 27017572.
2. Martinez-Botella; Gabriel (West Roxbury, MA), Hale; Michael (Bedford, MA), Maltais; Francois (Tewksbury, MA), Straub; Judith (Santa Cruz, CA), Tang; Qing (Acton, MA), Pyrrole inhibitors of ERK protein kinase, synthesis thereof and intermediates thereto, US7,354,939 (2008).
