Reference Detail

Ref Type
PMID
Authors S Buonamici, A Yoshimi, M Thomas, M Seiler, B Chan, B Caleb, R Darman, P Fekkes, C Karr, GF. Keaney, VM. Klimek, K Kunii, L Lee, SC Lee, X Liu, C Meeske, Y Mizui, E Padron, E Park, E Pazolli, S Prajapati, J Taylor, J Wang, M Warmuth, L Yu, P Zhu et. al.
Title H3B-8800, an Orally Bioavailable Modulator of the SF3b Complex, Shows Efficacy in Spliceosome-Mutant Myeloid Malignancies
Journal Blood 2016 128:966
Vol
Issue
Date
URL http://www.bloodjournal.org/content/128/22/966?sso-checked=true
Abstract Text Blood

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
H3B-8800 H3B-8800 binds to the SF3B complex and modulates splicing events, preferentially kills splicesome mutant tumor cells (Blood 2016 128: 966)
Variant Impact Protein Effect Variant Description Associated with drug Resistance
R1074H missense unknown SF3B1 R1074H lies within the HEAT repeat 9 region of the Sf3b1 protein (UniProt.org). R1074H has been demonstrated to mediate resistance to splicing modulators in culture (PMID: 28541300, PMID: 21981285, Blood 2016 128:966), but has not been biochemically characterized and therefore, its effect on Sf3b1 protein function is unknown (PubMed, Jan 2019). Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
SF3B1 K700E chronic myeloid leukemia sensitive H3B-8800 Preclinical - Cell line xenograft Actionable In a preclinical study, H3B-8800 inhibited tumor growth in cell line xenograft models of chronic myeloid leukemia harboring SF3B1 K700E while had no effect in SF3B1 wild-type controls (Blood 2016 128:966). detail...
KMT2A-MLLT3 SRSF2 P95H acute myeloid leukemia sensitive H3B-8800 Preclinical Actionable In a preclinical study, H3B-8800 inhibited tumor growth in transplant animal models of mouse acute myeloid leukemia cells harboring SRSF2 P95H and KMT2A-MLLT3 (MLL-AF9) while had no effect in SRSF2 wild-type controls (Blood 2016 128:966). detail...
SF3B1 K700E acute myeloid leukemia sensitive H3B-8800 Preclinical - Cell culture Actionable In a preclinical study, H3B-8800 preferentially inhibited growth of mouse acute myeloid leukemia cells harboring SF3B1 K700E compared to SF3B1 wild-type cells in culture (Blood 2016 128:966). detail...
Unknown unknown chronic myelomonocytic leukemia not applicable H3B-8800 Preclinical - Pdx Actionable In a preclinical study, H3B-8800 treatment reduced tumor burden in patient-derived xenograft (PDX) models of chronic myelomonocytic leukemia harboring spliceosome mutations but not spliceosome wild-type models (Blood 2016 128:966). detail...
SF3B1 R1074H Advanced Solid Tumor resistant H3B-8800 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing SF3B1 R1074H were resistant to H3B-8800 in culture (Blood 2016 128:966). detail...