Ulixertinib free base | VRT752271 | BVD-523 | CAS#869886-67-9 | CAS#1956366-10-1 | ERK Inhibitor

MedKoo Cat#: 406561 | Name: Ulixertinib (BVD-523)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Ulixertinib (BVD-523)

CAS#869886-67-9 (free base)

Theoretical Analysis

MedKoo Cat#: 406561

Name: Ulixertinib (BVD-523)

CAS#: 869886-67-9 (free base)

Chemical Formula: C21H22Cl2N4O2

Exact Mass: 432.1120

Molecular Weight: 433.33

Elemental Analysis: C, 58.21; H, 5.12; Cl, 16.36; N, 12.93; O, 7.38

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
100mg	USD 350.00	Ready to ship
500mg	USD 750.00	Ready to ship
1g	USD 1,150.00	Ready to ship
5g	USD 3,650.00	Ready to ship
10g	USD 4,950.00	Ready to ship

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Related CAS #

869886-67-9 (free base) 1956366-10-1 (HCl) 1975172-95-2 (HCl hydrate)

Synonym

BVD-523, BVD 523, BVD523, VRT752271, VRT752271, VRT 752271, Ulixertinib

IUPAC/Chemical Name

(S)-4-(5-chloro-2-(isopropylamino)pyridin-4-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-1H-pyrrole-2-carboxamide.

InChi Key

KSERXGMCDHOLSS-LJQANCHMSA-N

InChi Code

InChI=1S/C21H22Cl2N4O2/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)/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

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, not in water

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#XPR70221

QC Data

View QC data: current batch, Lot#XPR70221

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ulixertinib (BVD-523; VRT752271) is an ATP-competitive and reversible covalent 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:

This study infected 6-week-old female BALB/c mice with Chlamydia serovar D to determine whether BVD-523 could inhibit Chlamydia development in vivo. DMSO, AZM, BVD-523, and AZM + BVD-523 were administered orally from day 5 to day 8 after infection. Vaginal swabs were taken on days 5 and 8 for cell culture and to determine the number of inclusions. No difference in the number of infectious progeny was recorded between day 5 and day 8 cultures (P > 0.05) (Figure 6a). However, the number of progeny was greatly reduced in the AZM-, BVD-523‒, and AZM + BVD-523‒treated groups on day 8 (P < 0.05) (Figure 6b–d). These data demonstrated that BVD-523 could inhibit C. trachomatis replication in vivo. Reference: J Invest Dermatol. 2021 Apr;141(4):852-862.e6. https://www.jidonline.org/article/S0022-202X(20)32055-8/fulltext

	Solvent	mg/mL	mM
Solubility
	DMSO	93.0	214.62
	Ethanol	43.0	99.23

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 433.33 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. Xue Y, Chen W, Mai Z, Yu X, Wu Q, Wan C, Su X, Wu Y, Rong Z, Zheng H. Inhibition of the Extracellular Signal-Regulated Kinase/Ribosomal S6 Kinase Cascade Limits Chlamydia trachomatis Infection. J Invest Dermatol. 2021 Apr;141(4):852-862.e6. doi: 10.1016/j.jid.2020.07.033. Epub 2020 Sep 9. PMID: 32918951. 2. 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 3. Xue Y, Chen W, Mai Z, Yu X, Wu Q, Wan C, Su X, Wu Y, Rong Z, Zheng H. Inhibition of the Extracellular Signal-Regulated Kinase/Ribosomal S6 Kinase Cascade Limits Chlamydia trachomatis Infection. J Invest Dermatol. 2021 Apr;141(4):852-862.e6. doi: 10.1016/j.jid.2020.07.033. Epub 2020 Sep 9. PMID: 32918951. 4. 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:

In vivo protocol:

1: Itoh M, Tohda S. Effects of ERK1/2 Inhibitors on the Growth of Acute Leukemia Cells. Anticancer Res. 2024 Dec;44(12):5263-5270. doi: 10.21873/anticanres.17354. PMID: 39626905. 2: Yin F, Li F, Qi P, Zhang A. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma. Open Life Sci. 2024 Nov 12;19(1):20220980. doi: 10.1515/biol-2022-0980. PMID: 39588117; PMCID: PMC11588011. 3: Sugiyanto RN, Metzger C, Inal A, Truckenmueller F, Gür K, Eiteneuer E, Huth T, Fraas A, Heinze I, Kirkpatrick J, Sticht C, Albrecht T, Goeppert B, Poth T, Pusch S, Mehrabi A, Schirmacher P, Ji J, Ori A, Roessler S. Proteomic profiling reveals CEACAM6 function in driving gallbladder cancer aggressiveness through integrin receptor, PRKCD and AKT/ERK signaling. Cell Death Dis. 2024 Oct 28;15(10):780. doi: 10.1038/s41419-024-07171-x. PMID: 39468006; PMCID: PMC11519453. 4: Ge F, Wang Y, Chen P, Sharma A, Huang X, Dakal TC, Wang Z, Jaehde U, Essler M, Schmid M, Schmidt-Wolf IGH. FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia. Curr Med Chem. 2024 Oct 11. doi: 10.2174/0109298673311108240926062214. Epub ahead of print. PMID: 39400016. 5: Lei Y, Wang L, Liu P, Song Y, Gong Y, Jiang Y, Li S. Clarifying new molecular subtyping and precise treatment of melanoma based on disulfidptosis-related lncRNA signature. Eur J Med Res. 2024 Sep 28;29(1):468. doi: 10.1186/s40001-024-02035-8. PMID: 39342368; PMCID: PMC11438283. 6: Christen D, Lauinger M, Brunner M, Dengjel J, Brummer T. The mTOR pathway controls phosphorylation of BRAF at T401. Cell Commun Signal. 2024 Sep 2;22(1):428. doi: 10.1186/s12964-024-01808-2. PMID: 39223665; PMCID: PMC11370054. 7: Grogan L, Shapiro P. Progress in the development of ERK1/2 inhibitors for treating cancer and other diseases. Adv Pharmacol. 2024;100:181-207. doi: 10.1016/bs.apha.2024.04.001. Epub 2024 Apr 24. PMID: 39034052. 8: Vo KT, Sabnis AJ, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Jaju A, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, Parsons DW. Phase II Study of Ulixertinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Alterations: APEC1621J of the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial. JCO Precis Oncol. 2024 Jun;8:e2400103. doi: 10.1200/PO.24.00103. PMID: 38935895; PMCID: PMC11639582. 9: Sun Z, Ji Z, Meng H, He W, Li B, Pan X, Zhou Y, Yu G. Lactate facilitated mitochondrial fission-derived ROS to promote pulmonary fibrosis via ERK/DRP-1 signaling. J Transl Med. 2024 May 21;22(1):479. doi: 10.1186/s12967-024-05289-2. PMID: 38773615; PMCID: PMC11106888. 10: Shen S, Radhakrishnan SK, Harrell JC, Puchalapalli M, Koblinski J, Clevenger C. The Human Intermediate Prolactin Receptor I-tail Contributes Breast Oncogenesis by Targeting Ras/MAPK Pathway. Endocrinology. 2024 Apr 29;165(6):bqae039. doi: 10.1210/endocr/bqae039. PMID: 38713636; PMCID: PMC11492283. 11: Chen Y, Xiao X, Hu G, Liu R, Xue J. Antitumor activity of extracellular signal-regulated kinases 1/2 inhibitor BVD-523 (ulixertinib) on thyroid cancer cells. J Cancer Res Ther. 2024 Apr 1;20(2):570-577. doi: 10.4103/jcrt.jcrt_1504_23. Epub 2024 Apr 30. PMID: 38687926. 12: Buchbinder EI, Cohen JV, Tarantino G, Lian CG, Liu D, Haq R, Hodi FS, Lawrence DP, Giobbie-Hurder A, Knoerzer D, Sullivan RJ. A Phase II Study of ERK Inhibition by Ulixertinib (BVD-523) in Metastatic Uveal Melanoma. Cancer Res Commun. 2024 May 21;4(5):1321-1327. doi: 10.1158/2767-9764.CRC-24-0036. PMID: 38683104; PMCID: PMC11107576. 13: Pishdad R, Illei PB, Gocke CD, Ball DW. RET gene fusion and emergent Selpercatinib resistance in a calcitonin-rich neuroendocrine carcinoma: a case report. Front Oncol. 2024 Feb 14;14:1360492. doi: 10.3389/fonc.2024.1360492. PMID: 38469239; PMCID: PMC10926684. 14: De Ávila-Arias M, Villarreal-Camacho JL, Cadena-Cruz C, Hurtado-Gómez L, Costello HM, Rodriguez A, Burgos-Florez F, Bettin A, Kararoudi MN, Muñoz A, Peeples ME, San-Juan-Vergara H. Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase. Front Microbiol. 2024 Feb 16;15:1339569. doi: 10.3389/fmicb.2024.1339569. PMID: 38455070; PMCID: PMC10919290. 15: Mirzaie M, Gholizadeh E, Miettinen JJ, Ianevski F, Ruokoranta T, Saarela J, Manninen M, Miettinen S, Heckman CA, Jafari M. Designing patient-oriented combination therapies for acute myeloid leukemia based on efficacy/toxicity integration and bipartite network modeling. Oncogenesis. 2024 Mar 1;13(1):11. doi: 10.1038/s41389-024-00510-9. PMID: 38429288; PMCID: PMC10907624. 16: Sun Y, Cheng J, Nie D, Fang Q, Li C, Zhang Y. Metformin inhibits cell proliferation and ACTH secretion in AtT20 cells via regulating the MAPK pathway. Mol Cell Endocrinol. 2024 Mar 1;582:112140. doi: 10.1016/j.mce.2023.112140. Epub 2023 Dec 24. PMID: 38147953. 17: Tiong TY, Chan ML, Wang CH, Yadav VK, Pikatan NW, Fong IH, Yeh CT, Kuo KT, Huang WC. Exosomal miR-21 determines lung-to-brain metastasis specificity through the DGKB/ERK axis within the tumor microenvironment. Life Sci. 2023 Sep 15;329:121945. doi: 10.1016/j.lfs.2023.121945. Epub 2023 Jul 16. PMID: 37454756. 18: Liu SQ, Chen DY, Li B, Gao ZJ, Feng HF, Yu X, Liu Z, Wang Y, Li WG, Sun S, Sun SR, Wu Q. Single-cell analysis of white adipose tissue reveals the tumor- promoting adipocyte subtypes. J Transl Med. 2023 Jul 15;21(1):470. doi: 10.1186/s12967-023-04256-7. PMID: 37454080; PMCID: PMC10349475. 19: Tian Y, Zhang M, Heng P, Hou H, Wang B. Pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation for identification of potential ERK inhibitors. J Biomol Struct Dyn. 2024 Feb- Mar;42(4):2153-2161. doi: 10.1080/07391102.2023.2204495. Epub 2023 May 2. PMID: 37129289. 20: Baek MJ, Nguyen DT, Kim D, Yoo SY, Lee SM, Lee JY, Kim DD. Tailoring renal- clearable zwitterionic cyclodextrin for colorectal cancer-selective drug delivery. Nat Nanotechnol. 2023 Aug;18(8):945-956. doi: 10.1038/s41565-023-01381-8. Epub 2023 Apr 27. PMID: 37106052.