Fig. 4: Chronic exposure leads to acquired resistance to BSJ-4-116 mediated by G-loop mutations. | Nature Chemical Biology

Fig. 4: Chronic exposure leads to acquired resistance to BSJ-4-116 mediated by G-loop mutations.

From: Discovery and resistance mechanism of a selective CDK12 degrader

Fig. 4: Chronic exposure leads to acquired resistance to BSJ-4-116 mediated by G-loop mutations.The alternative text for this image may have been generated using AI.

a, Immunoblots for CDK12 and GPADH in parental and resistant Jurkat and MOLT-4 cells treated with BSJ-4-116 and BSJ-4-23, at the indicated concentrations for 6 h. Data represent n = 2 independent experiments. b, Dose–response curves for parental and resistant Jurkat and MOLT-4 cells treated with BSJ-4-116 at the indicated dose range for 72 h. Data are presented as mean ± s.d. of n = 3 biologically independent samples and represent n = 2 independent experiments. c, Detection of heterozygous Ile733Val mutation in MOLT-4-resistant cells. DNA chromatograms of Sanger sequencing show the region of mutation from PCR-amplified CDK12 complementary DNA.

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