c-Myc is an oncogenic transcriptional factor driving tumor initiation, progression and poor prognosis in 80% of all tumor types, especially in B-cell malignancies and small cell lung cancer (SCLC) with Myc genomic alterations. Myc dysregulation have been directly linked to the poor clinical outcome in these cancers. Therefore, it is highly warranted to discover and develop novel Myc therapeutical agents for targeting Myc driven cancers. Here we described GT19630, a GSPT1/Myc CELMoD. GT19630 was discovered through an SAR effort for c-Myc degrader by using c-Myc ELISA and Western blot assays in c-Myc driven HL60 AML cells. GT19630 selectively degraded c-Myc proteins in HL60 cells as compared to growth-factor regulated c-Myc erythroid progenitor cells. GT19630 was then confirmed to selective degradation of CELMoD targets, GSPT1/GSPT2 (translation termination factor G1 to S phase transition proteins 1 and 2). Further, GT19630 inhibited the cell proliferation with IC50<10 nM in 74% B-cell malignant cell lines (20/27) bearing deregulated c-Myc and in 79% of SCLC cell lines (4/19) carrying deregulated Myc (c-Myc, N-Myc or L-Myc) tested. Moreover, GT19630 completely degraded Myc proteins in AML, lymphoma and multiple myeloma (c-Myc) and SCLC (c-Myc and N-Myc) xenograft tumors at the lowest dose of 1.0 mg/kg and induced complete tumor regression (lowest dose=0.3 mg/kg) tested. Furthermore, this compound eradicated lymphoma cells in Daudi-induced liquid lymphoma mouse models. In addition, GT19630, as a potent GSPT1/Myc CELMoD, demonstrated an even-driven pharmacology in vivo and induced complete tumor regression with a dosing regimen of 3 day on/7 day off. Remarkably, GT19630 selectively degraded Myc proteins in HL60 and DMS114 SCLC xenograft tumors as compared to a much less potency at degrading c-Myc in rat spleen. Finally, GT19630 demonstrated favorable PK and safety profiles (an 8-fold safety therapeutic windows) with no effect on myeloid lineages in rats at the dose of 5 mg/kg for 14 days, indicating GT19630 lacks myelosuppression as reported for other CELMoDs. Currently, GT19630 has been advanced into IND enabling stage.