H3B-8800 | CAS#1825302-42-8 | SF3b Modulator

MedKoo Cat#: 564003 | Name: H3B-8800

Featured

Description:

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

H3B-8800, also known as RVT-2001, is an orally available small-molecule splicing modulator (SF3b Modulator). H3B-8800 induces lethality in spliceosome-mutant cancers. H3B-8800 potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells. These killing effects of H3B-8800 are due to its direct interaction with the SF3b complex, as evidenced by loss of H3B-8800 activity in drug-resistant cells bearing mutations in genes encoding SF3b components. H3B-8800 displayed preferential lethality towards SF3B1-mutated cells and synergism with the BCL2 inhibitor venetoclax, supporting the potential use of SF3B1 inhibitors as a novel therapeutic strategy in CLL.

Chemical Structure

H3B-8800

CAS#1825302-42-8

Theoretical Analysis

MedKoo Cat#: 564003

Name: H3B-8800

CAS#: 1825302-42-8

Chemical Formula: C31H45N3O6

Exact Mass: 555.3308

Molecular Weight: 555.72

Elemental Analysis: C, 67.00; H, 8.16; N, 7.56; O, 17.27

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 750.00	2 Weeks
5mg	USD 1,650.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1825302-42-8

Synonym

H3B-8800; H3B8800; H3B 8800; RVT-2001; RVT 2001; RVT2001;

IUPAC/Chemical Name

(2S,3S,6S,7R,10R,E)-7,10-Dihydroxy-3,7-dimethyl-12-oxo-2-((R,2E,4E)-6-(pyridin-2-yl)hepta-2,4-dien-2-yl)oxacyclododec-4-en-6-yl 4-methylpiperazine-1-carboxylate

InChi Key

YOIQWBAHJZGRFW-WVRLKXNASA-N

InChi Code

InChI=1S/C31H45N3O6/c1-22(26-11-6-7-16-32-26)9-8-10-23(2)29-24(3)12-13-27(39-30(37)34-19-17-33(5)18-20-34)31(4,38)15-14-25(35)21-28(36)40-29/h6-13,16,22,24-25,27,29,35,38H,14-15,17-21H2,1-5H3/b9-8+,13-12+,23-10+/t22-,24+,25-,27+,29-,31-/m1/s1

SMILES Code

O=C(N1CCN(C)CC1)O[C@H]([C@](C)(O)CC[C@@H](O)C2)/C=C/[C@H](C)[C@@H](/C(C)=C/C=C/[C@H](C3=NC=CC=C3)C)OC2=O

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

>3 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

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs)

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 555.72 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

1: López-Oreja I, Gohr A, Playa-Albinyana H, Giró A, Arenas F, Higashi M, Tripathi R, López-Guerra M, Irimia M, Aymerich M, Valcárcel J, Bonnal S, Colomer D. SF3B1 mutation-mediated sensitization to H3B-8800 splicing inhibitor in chronic lymphocytic leukemia. Life Sci Alliance. 2023 Aug 10;6(11):e202301955. doi: 10.26508/lsa.202301955. PMID: 37562845; PMCID: PMC10415613. 2: Morales ML, García-Vicente R, Rodríguez-García A, Reyes-Palomares A, Vincelle-Nieto Á, Álvarez N, Ortiz-Ruiz A, Garrido-García V, Giménez A, Carreño- Tarragona G, Sánchez R, Ayala R, Martínez-López J, Linares M. Posttranslational splicing modifications as a key mechanism in cytarabine resistance in acute myeloid leukemia. Leukemia. 2023 Aug;37(8):1649-1659. doi: 10.1038/s41375-023-01963-4. Epub 2023 Jul 8. PMID: 37422594; PMCID: PMC10400425. 3: Spinello A, Borišek J, Malcovati L, Magistrato A. Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers. Int J Mol Sci. 2021 Oct 18;22(20):11222. doi: 10.3390/ijms222011222. PMID: 34681880; PMCID: PMC8540225. 4: Sim J, Jang E, Kim HJ, Jeon H. Total Syntheses of Pladienolide-Derived Spliceosome Modulators. Molecules. 2021 Sep 30;26(19):5938. doi: 10.3390/molecules26195938. PMID: 34641481; PMCID: PMC8512135. 5: Steensma DP, Wermke M, Klimek VM, Greenberg PL, Font P, Komrokji RS, Yang J, Brunner AM, Carraway HE, Ades L, Al-Kali A, Alonso-Dominguez JM, Alfonso-Piérola A, Coombs CC, Deeg HJ, Flinn I, Foran JM, Garcia-Manero G, Maris MB, McMasters M, Micol JB, De Oteyza JP, Thol F, Wang ES, Watts JM, Taylor J, Stone R, Gourineni V, Marino AJ, Yao H, Destenaves B, Yuan X, Yu K, Dar S, Ohanjanian L, Kuida K, Xiao J, Scholz C, Gualberto A, Platzbecker U. Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms. Leukemia. 2021 Dec;35(12):3542-3550. doi: 10.1038/s41375-021-01328-9. Epub 2021 Jun 25. PMID: 34172893; PMCID: PMC8632688. 6: Rhoades D, Rheingold AL, O'Malley BW, Wang J. Expedient Total Syntheses of Pladienolide-Derived Spliceosome Modulators. J Am Chem Soc. 2021 Apr 7;143(13):4915-4920. doi: 10.1021/jacs.1c01135. Epub 2021 Mar 23. PMID: 33755462. 7: Saygin C, Carraway HE. Current and emerging strategies for management of myelodysplastic syndromes. Blood Rev. 2021 Jul;48:100791. doi: 10.1016/j.blre.2020.100791. Epub 2020 Dec 27. PMID: 33423844. 8: Zhang D, Meng F. A Comprehensive Overview of Structure-Activity Relationships of Small-Molecule Splicing Modulators Targeting SF3B1 as Anticancer Agents. ChemMedChem. 2020 Nov 18;15(22):2098-2120. doi: 10.1002/cmdc.202000642. Epub 2020 Oct 22. PMID: 33037739. 9: Zhou Y, Han C, Wang E, Lorch AH, Serafin V, Cho BK, Gutierrez Diaz BT, Calvo J, Fang C, Khodadadi-Jamayran A, Tabaglio T, Marier C, Kuchmiy A, Sun L, Yacu G, Filip SK, Jin Q, Takahashi YH, Amici DR, Rendleman EJ, Rawat R, Bresolin S, Paganin M, Zhang C, Li H, Kandela I, Politanska Y, Abdala-Valencia H, Mendillo ML, Zhu P, Palhais B, Van Vlierberghe P, Taghon T, Aifantis I, Goo YA, Guccione E, Heguy A, Tsirigos A, Wee KB, Mishra RK, Pflumio F, Accordi B, Basso G, Ntziachristos P. Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia. Cancer Discov. 2020 Sep;10(9):1388-1409. doi: 10.1158/2159-8290.CD-19-1436. Epub 2020 May 22. PMID: 32444465; PMCID: PMC7483384. 10: Eymin B. Targeting the spliceosome machinery: A new therapeutic axis in cancer? Biochem Pharmacol. 2021 Jul;189:114039. doi: 10.1016/j.bcp.2020.114039. Epub 2020 May 15. PMID: 32417188. 11: Rioux N, Smith S, Colombo F, Kim A, Lai WG, Nix D, Siu YA, Schindler J, Smith PG. Metabolic disposition of H3B-8800, an orally available small-molecule splicing modulator, in rats, monkeys, and humans. Xenobiotica. 2020 Sep;50(9):1101-1114. doi: 10.1080/00498254.2019.1709134. Epub 2020 Jan 6. PMID: 31902291. 12: Pellagatti A, Boultwood J. Splicing factor mutant myelodysplastic syndromes: Recent advances. Adv Biol Regul. 2020 Jan;75:100655. doi: 10.1016/j.jbior.2019.100655. Epub 2019 Sep 19. PMID: 31558432. 13: Aujla A, Linder K, Iragavarapu C, Karass M, Liu D. SRSF2 mutations in myelodysplasia/myeloproliferative neoplasms. Biomark Res. 2018 Sep 26;6:29. doi: 10.1186/s40364-018-0142-y. PMID: 30275952; PMCID: PMC6158887. 14: Steensma DP. An RNA bestiary in splicing-mutant MDS. Blood. 2018 Sep 20;132(12):1217-1219. doi: 10.1182/blood-2018-07-859942. PMID: 30237252. 15: A Small-Molecule Splicing Modulator Targets Spliceosome-Mutant Cells. Cancer Discov. 2018 Apr;8(4):384. doi: 10.1158/2159-8290.CD-RW2018-038. Epub 2018 Mar 2. PMID: 29500297. 16: Finci LI, Zhang X, Huang X, Zhou Q, Tsai J, Teng T, Agrawal A, Chan B, Irwin S, Karr C, Cook A, Zhu P, Reynolds D, Smith PG, Fekkes P, Buonamici S, Larsen NA. The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action. Genes Dev. 2018 Feb 1;32(3-4):309-320. doi: 10.1101/gad.311043.117. PMID: 29491137; PMCID: PMC5859971. 17: Seiler M, Yoshimi A, Darman R, Chan B, Keaney G, Thomas M, Agrawal AA, Caleb B, Csibi A, Sean E, Fekkes P, Karr C, Klimek V, Lai G, Lee L, Kumar P, Lee SC, Liu X, Mackenzie C, Meeske C, Mizui Y, Padron E, Park E, Pazolli E, Peng S, Prajapati S, Taylor J, Teng T, Wang J, Warmuth M, Yao H, Yu L, Zhu P, Abdel- Wahab O, Smith PG, Buonamici S. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat Med. 2018 May;24(4):497-504. doi: 10.1038/nm.4493. Epub 2018 Feb 19. PMID: 29457796; PMCID: PMC6730556. 18: Montalban-Bravo G, Garcia-Manero G, Jabbour E. Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes. Curr Opin Hematol. 2018 Mar;25(2):146-153. doi: 10.1097/MOH.0000000000000400. PMID: 29266015.