H3B-8800

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| image = H3B-8800.svg

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| CAS_number = 1825302-42-8

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| PubChem = 92135969

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| IUPAC_name = [(2S,3S,4E,6S,7R,10R)-7,10-dihydroxy-3,7-dimethyl-12-oxo-2-[(2E,4E,6R)-6-pyridin-2-ylhepta-2,4-dien-2-yl]-1-oxacyclododec-4-en-6-yl] 4-methylpiperazine-1-carboxylate

| C = 31

| H = 45

| N = 3

| O = 6

| SMILES = C[C@H]1/C=C/[C@@H]([C@](CC[C@H](CC(=O)O[C@@H]1/C(=C/C=C/[C@@H](C)C2=CC=CC=N2)/C)O)(C)O)OC(=O)N3CCN(CC3)C

| StdInChI = 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

| StdInChIKey = YOIQWBAHJZGRFW-WVRLKXNASA-N

}}

H3B-8800 is an experimental drug which acts as an inhibitor of the SF3B1 protein, which forms part of the splicing factor 3b protein complex. This is commonly mutated in some forms of cancer, principally leukemia but also some subtypes of breast cancer and melanoma. H3B-8800 has reached early stage human clinical trials in patients whose cancers express mutations that make them susceptible to inhibition of SF3B1.{{cite journal | vauthors = 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 | title = The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action | journal = Genes & Development | volume = 32 | issue = 3–4 | pages = 309–320 | date = February 2018 | pmid = 29491137 | doi = 10.1101/gad.311043.117 | pmc = 5859971 }}{{cite journal | vauthors = 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 | title = H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers | journal = Nature Medicine | volume = 24 | issue = 4 | pages = 497–504 | date = May 2018 | pmid = 29457796 | doi = 10.1038/nm.4493 | pmc = 6730556 }}{{cite journal | vauthors = 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 | title = Posttranslational Regulation of the Exon Skipping Machinery Controls Aberrant Splicing in Leukemia | journal = Cancer Discovery | volume = 10 | issue = 9 | pages = 1388–1409 | date = September 2020 | pmid = 32444465 | doi = 10.1158/2159-8290.CD-19-1436 | pmc = 7483384 }}{{cite journal | vauthors = Zhang D, Meng F | title = A Comprehensive Overview of Structure-Activity Relationships of Small-Molecule Splicing Modulators Targeting SF3B1 as Anticancer Agents | journal = ChemMedChem | volume = 15 | issue = 22 | pages = 2098–2120 | date = November 2020 | pmid = 33037739 | doi = 10.1002/cmdc.202000642 }}{{cite journal | vauthors = Sim J, Jang E, Kim HJ, Jeon H | title = Total Syntheses of Pladienolide-Derived Spliceosome Modulators | journal = Molecules | volume = 26 | issue = 19 | date = September 2021 | page = 5938 | pmid = 34641481 | doi = 10.3390/molecules26195938 | doi-access = free | pmc = 8512135 }}{{cite journal | vauthors = Eymin B | title = Targeting the spliceosome machinery: A new therapeutic axis in cancer? | journal = Biochemical Pharmacology | volume = 189 | pages = 114039 | date = July 2021 | pmid = 32417188 | doi = 10.1016/j.bcp.2020.114039 }}{{cite journal | vauthors = Spinello A, Borišek J, Malcovati L, Magistrato A | title = Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers | journal = International Journal of Molecular Sciences | volume = 22 | issue = 20 | date = October 2021 | page = 11222 | pmid = 34681880 | doi = 10.3390/ijms222011222 | doi-access = free | pmc = 8540225 }}{{cite journal | vauthors = 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 | title = Phase I First-in-Human Dose Escalation Study of the oral SF3B1 modulator H3B-8800 in myeloid neoplasms | journal = Leukemia | volume = 35 | issue = 12 | pages = 3542–3550 | date = December 2021 | pmid = 34172893 | doi = 10.1038/s41375-021-01328-9 | pmc = 8632688 }}{{cite journal | vauthors = Wheeler EC, Martin BJ, Doyle WC, Neaher S, Conway CA, Pitton CN, Gorelov RA, Donahue M, Jann JC, Abdel-Wahab O, Taylor J, Seiler M, Buonamici S, Pikman Y, Garcia JS, Belizaire R, Adelman K, Tothova Z | title = Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML | journal = Science Translational Medicine | volume = 16 | issue = 728 | pages = eade2774 | date = January 2024 | pmid = 38170787 | doi = 10.1126/scitranslmed.ade2774 | pmc = 11222919 }}