Structure of CBL0137
CAS No.: 1197996-80-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
CBL-0137 is a metabolically stable curaxin that activates p53 with an EC50 value of 0.37 µM and inhibits NF-κB with an EC50 of 0.47 µM. It functionally inactivates the facilitates chromatin transcription complex (FACT), driving the effects on p53 and NF-κB and promoting cancer cell death.
Synonyms: Curaxin 137; CBL-C137
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 1197996-80-7 |
Formula : | C21H24N2O2 |
M.W : | 336.43 |
SMILES Code : | CC(NCCN1C2=C(C3=C1C=CC(C(C)=O)=C3)C=C(C(C)=O)C=C2)C |
Synonyms : |
Curaxin 137; CBL-C137
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MDL No. : | MFCD18071578 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Description |
CBL0137 is a suppressor of the histone chaperone FACT, which is crucial for chromatin transcription. By downregulating NF-kappaB and activating p53, CBL0137 effectively reinstates acetylation and trimethylation of histone H3. Its role as an anticancer agent is further underscored by its ability to trigger apoptosis in cancer cells[1].
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In Vitro:
Concentration | Treated Time | Description | References |
D425 cells | 1 µM | 24 hours | Inhibited cell proliferation and induced apoptosis | Cell Death Dis. 2020 Dec 2;11(12):1029. |
ONS-76 cells | 2 µM | 1 hour | Enhanced sensitivity to cisplatin and radiation, reduced cell viability | Cancer Lett. 2021 Nov 1;520:201-212. |
HD-MB03 cells | 2 µM | 1 hour | Enhanced sensitivity to cisplatin and radiation, reduced cell viability | Cancer Lett. 2021 Nov 1;520:201-212. |
A1207 | 0.6 or 2.0 µM | 1 or 16 hours | Evaluate the effect of CBL0137 on FACT, p53, and NF-ĸB. Results showed that CBL0137 caused loss of FACT subunits from the soluble protein fraction, significantly increased p53 expression, and downregulated NF-ĸB-dependent transcription. | Neuro Oncol. 2017 Feb 1;19(2):186-196. |
U87MG | 0.6 or 2.0 µM | 1 or 16 hours | Evaluate the effect of CBL0137 on FACT, p53, and NF-ĸB. Results showed that CBL0137 caused loss of FACT subunits from the soluble protein fraction, significantly increased p53 expression, and downregulated NF-ĸB-dependent transcription. | Neuro Oncol. 2017 Feb 1;19(2):186-196. |
HT1080 cells | 1-2.5 µM | 15 minutes | To evaluate the effect of CBL0137 on enhancer-promoter communication (EPC), results showed that CBL0137 significantly decreased transcript yield on both chromatinized and histone-free DNA templates. | Nat Commun. 2019 Mar 29;10(1):1441. |
B16 NF-κB-Luc reporter cells | 5 or 10 µM | 15 minutes | To evaluate the inhibitory effect of CBL0137 on NF-κB pathway activity. Results showed that CBL0137 dose-dependently suppressed NF-κB pathway activity. | Cancer Res. 2016 Nov 15;76(22):6620-6630. |
KELLY cells | 25 µM | 15 minutes | Evaluate the effect of CBL0137 and PNB on chromatin condensation | Clin Cancer Res. 2021 Aug 1;27(15):4338-4352. |
RCC45 | 2 µM | 24 hours | Evaluate the effect of CBL0137 on the cell cycle of RCC45 cells | Sci Transl Med. 2011 Aug 10;3(95):95ra74. |
HDMB03 cells | 1 µM | 24 hours | Inhibited cell proliferation and induced apoptosis | Cell Death Dis. 2020 Dec 2;11(12):1029. |
D458 cells | 1 µM | 24 hours | Inhibited cell proliferation and induced apoptosis | Cell Death Dis. 2020 Dec 2;11(12):1029. |
B16 melanoma cells | 0.7, 1.4, 2.8, or 5.6 µM | 15 or 30 minutes | To evaluate the in vitro cytotoxic effects of CBL0137 on B16 melanoma cells. Results showed that CBL0137 significantly reduced tumor cell viability at both 15 and 30 minutes of treatment in a dose-dependent manner. | Cancer Res. 2016 Nov 15;76(22):6620-6630. |
BE(2)-C cells | 100 nM, 200 nM | 20 hours | Evaluate the effect of CBL0137 on PNB-induced DNA damage repair | Clin Cancer Res. 2021 Aug 1;27(15):4338-4352. |
Murine Embryonic Fibroblasts (MEFs) | 5 µM | 24 hours | CBL0137 induced ZBP1-dependent cell death by triggering Z-DNA formation and activating ZBP1-mediated necroptosis. | Nature. 2022 Jun;606(7914):594-602. |
NK-92 cells | 500 nM | 24 hours | To investigate the effect of CBL0137 on NK cell activation, results showed that CBL0137 significantly enhanced NK cell-mediated killing function. | Nucleic Acids Res. 2022 Aug 26;50(15):8700-8718. |
HeLa cells | 500 nM | 24 hours | To investigate the inhibitory effect of CBL0137 on ZIKV and influenza A virus infection, results showed that CBL0137 effectively inhibited viral infection. | Nucleic Acids Res. 2022 Aug 26;50(15):8700-8718. |
HEK293T cells | 100, 200, 500 nM | 24 hours | To investigate the induction of IFN signaling by CBL0137, results showed that CBL0137 significantly increased the expression of IFNs and ISGs. | Nucleic Acids Res. 2022 Aug 26;50(15):8700-8718. |
NDFs | 0.5 µM | 24 hours | To evaluate the effect of CBL0137 on the transcriptome of normal dermal fibroblasts. Results showed that CBL0137 at 0.5 μM induced widespread transcriptional changes, which were similar in p53-positive and negative cells. | Nucleic Acids Res. 2023 Nov 27;51(21):11836-11855. |
HT1080 | 0.5 µM | 24 hours | To evaluate the effect of CBL0137 on the transcriptome of HT1080 cells. Results showed that CBL0137 at 0.5 μM induced widespread transcriptional changes, which were similar in p53-positive and negative cells. | Nucleic Acids Res. 2023 Nov 27;51(21):11836-11855. |
NDFs | 1 µM | 24 hours | To evaluate the toxicity of CBL0137 on normal dermal fibroblasts and its effect on p53 activation. Results showed that CBL0137 induced p53 protein accumulation at concentrations of 0.5-1 μM and caused cell death at higher concentrations. | Nucleic Acids Res. 2023 Nov 27;51(21):11836-11855. |
HT1080 | 1 µM | 24 hours | To evaluate the toxicity of CBL0137 on HT1080 cells and its effect on p53 activation. Results showed that CBL0137 induced p53 protein accumulation at concentrations of 0.5-1 μM and caused cell death at higher concentrations. | Nucleic Acids Res. 2023 Nov 27;51(21):11836-11855. |
Jeko-1 | 0.5-2.0 µM | 24 hours | To evaluate the inhibitory effect of CBL0137 on B-NHL cell proliferation, results showed that CBL0137 significantly inhibited B-NHL cell proliferation in a concentration and time-dependent manner. | Cell Commun Signal. 2023 Jan 23;21(1):16. |
Raji | 0.5-2.0 µM | 24 hours | To evaluate the inhibitory effect of CBL0137 on B-NHL cell proliferation, results showed that CBL0137 significantly inhibited B-NHL cell proliferation in a concentration and time-dependent manner. | Cell Commun Signal. 2023 Jan 23;21(1):16. |
Farage | 0.5-2.0 µM | 24 hours | To evaluate the inhibitory effect of CBL0137 on B-NHL cell proliferation, results showed that CBL0137 significantly inhibited B-NHL cell proliferation in a concentration and time-dependent manner. | Cell Commun Signal. 2023 Jan 23;21(1):16. |
SU-DHL-4 | 0.5-2.0 µM | 24 hours | To evaluate the inhibitory effect of CBL0137 on B-NHL cell proliferation, results showed that CBL0137 significantly inhibited B-NHL cell proliferation in a concentration and time-dependent manner. | Cell Commun Signal. 2023 Jan 23;21(1):16. |
BJ fibroblasts | 1 µM | 3 hours | Induced degradation of POLR2A without affecting POLR1A degradation | Nucleic Acids Res. 2024 May 8;52(8):4151-4166. |
U2OS cells | 1 µM | 3 hours | Induced degradation of POLR2A, with a progressive consumption of form IIa and reduction in Ser5 and Ser2 phosphorylation of POLR2A | Nucleic Acids Res. 2024 May 8;52(8):4151-4166. |
Human Fibroblasts (HS68) | 5 µM | 36 hours | CBL0137 induced Z-DNA formation and ZBP1-dependent cell death in HS68 cells. | Nature. 2022 Jun;606(7914):594-602. |
MB52 | 300 nM | 48 hours | To evaluate the effect of CBL0137 on apoptosis and cell cycle in DPM cells, results showed that CBL0137 induced apoptosis and G2-M phase cell cycle arrest. | J Exp Clin Cancer Res. 2023 Nov 16;42(1):304. |
H2373 | 300 nM | 48 hours | To evaluate the effect of CBL0137 on NF-κB and p53, results showed that CBL0137 inhibited NF-κB and activated p53. | J Exp Clin Cancer Res. 2023 Nov 16;42(1):304. |
T. brucei Lister 427 | 0.038 µM | 48 hours | Evaluate the inhibitory activity of CBL0137 against T. brucei, with an EC50 of 0.038 μM. | J Med Chem. 2023 Feb 9;66(3):1972-1989. |
Non-cancerous ovarian epithelial cells (HOSE6.3, HOSE17.1) | 0-2.5 µM | 6 days | Evaluate the growth inhibitory activity of CBL0137 on non-cancerous ovarian epithelial cells, showing no significant growth inhibitory effect. | J Exp Clin Cancer Res. 2022 Dec 21;41(1):355. |
Patient-derived tumor cells (DF20, DF68, DF86, DF101, DF106, DF149, DF181) | 0-2.5 µM | 6 days | Evaluate the growth inhibitory activity of CBL0137 on patient-derived tumor cells, showing significant anti-growth activity against SSRP1-high tumor cells with IC50 values of 0.3–1.3 μM. | J Exp Clin Cancer Res. 2022 Dec 21;41(1):355. |
HGSC cell lines (OVCAR-8, OVCAR-4, OVCAR-3, Kuramochi, CAOV3, OV90, OAW42, PEO1, PEO4) | 0-2.5 µM | 6 days | Evaluate the growth inhibitory activity of CBL0137 on HGSC cell lines, showing significant anti-growth activity against SSRP1-high HGSC cell lines with IC50 values of 0.2–0.6 μM. | J Exp Clin Cancer Res. 2022 Dec 21;41(1):355. |
HeLa | 2 µM | 6 hours | Evaluate the effect of CBL0137 on DNA damage in HeLa cells | Sci Transl Med. 2011 Aug 10;3(95):95ra74. |
MM1.S cells | 0.3-3 µM | 6 hours | To analyze the effect of CBL0137 on gene expression profiles, results showed that CBL0137 strongly inhibited transcription regulated by enhancers or super-enhancers. | Nat Commun. 2019 Mar 29;10(1):1441. |
GBM 08-387 | 150 nM | 6 hours | Evaluate the effect of CBL0137 combined with radiotherapy on cell growth, results showed that combination treatment significantly reduced cell growth | Cancer Lett. 2021 Feb 28;499:232-242. |
GBM 3691 | 150 nM | 6 hours | Evaluate the effect of CBL0137 combined with radiotherapy on cell growth, results showed that combination treatment significantly reduced cell growth | Cancer Lett. 2021 Feb 28;499:232-242. |
GBM 1016 | 150 nM | 6 hours | Evaluate the effect of CBL0137 combined with radiotherapy on cell growth, results showed that combination treatment reduced cell growth but did not reach statistical significance | Cancer Lett. 2021 Feb 28;499:232-242. |
GBM NU757 | 150 nM | 6 hours | Evaluate the effect of CBL0137 combined with radiotherapy on cell growth, results showed that combination treatment significantly reduced cell growth | Cancer Lett. 2021 Feb 28;499:232-242. |
Non-stem tumor cells (NSTCs) | 100-600 nM | 72 hours | To evaluate the cytotoxic effect of CBL0137 on NSTCs, results showed NSTCs were also sensitive to CBL0137 but less so than GSCs. | Cancer Res. 2016 Apr 15;76(8):2432-42. |
GBM stem cells (GSCs) | 100-600 nM | 72 hours | To evaluate the cytotoxic effect of CBL0137 on GSCs, results showed GSCs were highly sensitive to CBL0137. | Cancer Res. 2016 Apr 15;76(8):2432-42. |
H2052 | 200-380 nM | 72 hours | To evaluate the killing effect of CBL0137 on DPM cells, results showed that CBL0137 effectively killed DPM cells at low concentrations. | J Exp Clin Cancer Res. 2023 Nov 16;42(1):304. |
H526 non-TICs | 250 nM | 72 hours | Evaluate the effect of CBL0137 combined with Rova-T on cell survival of H526 non-TICs, results showed no additional effect on non-TICs | Br J Cancer. 2021 Mar;124(5):893-895. |
H82 non-TICs | 250 nM | 72 hours | Evaluate the effect of CBL0137 combined with Rova-T on cell survival of H82 non-TICs, results showed no additional effect on non-TICs | Br J Cancer. 2021 Mar;124(5):893-895. |
HT1080 | 0.8 µM | 8 hours | Evaluate the p53 activation effect of CBL0137 on HT1080 cells | Sci Transl Med. 2011 Aug 10;3(95):95ra74. |
H526 TICs | 250 nM | 72 hours | Evaluate the effect of CBL0137 combined with Rova-T on cell survival of H526 TICs, results showed significant reduction in cell survival | Br J Cancer. 2021 Mar;124(5):893-895. |
H82 TICs | 250 nM | 72 hours | Evaluate the effect of CBL0137 combined with Rova-T on cell survival of H82 TICs, results showed significant reduction in cell survival | Br J Cancer. 2021 Mar;124(5):893-895. |
HCT116-p53 null | 1 µM | 8 hours | Evaluate the activation effect of CBL0137 on p53 mutants in HCT116-p53 null cells | Sci Transl Med. 2011 Aug 10;3(95):95ra74. |
In Vivo:
Administration | Dosage | Frequency | Description | References |
C57BL/6 mice | B16 melanoma subcutaneous xenograft model | Isolated limb perfusion (ILP), intravenous injection (i.v.), or intra-arterial infusion (IAI) | 0.1, 0.25, 0.5 or 1 mg (ILP); 80 mg/kg (i.v.) | Single 15 or 30 minutes (ILP); Single or once weekly for up to 4 weeks (i.v.) | To evaluate the antitumor efficacy and toxicity of CBL0137 via different administration routes in a B16 melanoma model. Results showed that CBL0137 delivered by ILP exhibited antitumor activity comparable to melphalan at doses corresponding to only a fraction of the systemic MTD, with lower toxicity. Intra-arterial infusion (IAI) of CBL0137 also demonstrated significant antitumor efficacy and safety. | Cancer Res. 2016 Nov 15;76(22):6620-6630. |
NSG mice | Orthotopic GBM model | Oral | 0.5 mg/mL | Replaced every 7 days, continuous treatment | To evaluate the therapeutic effect of CBL0137 on GBM mouse models, results showed CBL0137 significantly prolonged survival. | Cancer Res. 2016 Apr 15;76(8):2432-42. |
Nude mice | Subcutaneous and orthotopic GBM models | Intraperitoneal (subcutaneous), intravenous (orthotopic) | 10 mg/kg (subcutaneous), 70 mg/kg (orthotopic) | Daily for 7 days (subcutaneous); once a week for four weeks (orthotopic) | Evaluate the effect of CBL0137 combined with radiotherapy on survival and cancer stem cell frequency, results showed that combination treatment significantly prolonged survival and reduced cancer stem cell frequency | Cancer Lett. 2021 Feb 28;499:232-242. |
NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice | Subcutaneous xenograft model | Oral gavage | 20 mg/kg | Twice a week for 3 weeks | To evaluate the anti-tumor effect of CBL0137 in vivo, results showed that CBL0137 significantly suppressed tumor growth and prolonged survival. | J Exp Clin Cancer Res. 2023 Nov 16;42(1):304. |
C57BL/6J mice | B16-F10 melanoma model | Intratumoral injection | 20 μM | Every two days for a total of 4 doses | CBL0137 significantly reversed immune checkpoint blockade (ICB) unresponsiveness by inducing ZBP1-dependent necroptosis in fibroblasts of the tumor microenvironment (TME). | Nature. 2022 Jun;606(7914):594-602. |
Nude mice | Orthotopic U87MG and A1207 glioblastoma models | Oral or intravenous | 25 mg/kg orally, 70 or 90 mg/kg intravenously | Various regimens: oral daily, intravenous every 4 days or once weekly for 4 weeks | Evaluate the therapeutic effect of CBL0137 on glioblastoma. Results showed that intravenous administration of CBL0137 significantly prolonged survival, increased tumor cell apoptosis, and suppressed proliferation. Oral administration showed limited efficacy. | Neuro Oncol. 2017 Feb 1;19(2):186-196. |
Mice | Human tumor xenograft model | Oral gavage | 30 mg/kg | 5 days on/2 days off schedule for up to 4 weeks | Evaluate the antitumor effect of CBL0137 in mouse xenograft models | Sci Transl Med. 2011 Aug 10;3(95):95ra74. |
Nude mice | Mammary fat pad injection model | Oral gavage | 30 mg/kg | Five days a week for six weeks | Evaluate the inhibitory effect of CBL0137 on TONSL-amplified breast cancer cell lines in vivo | Cancer Res. 2023 Apr 14;83(8):1345-1360 |
Nude mice | Subcutaneous tumor xenograft model | Intraperitoneal injection | 30 mg/kg CBL0137 and 2 mg/kg cisplatin | Every other day for four weeks | Significantly suppressed MB tumor growth | Cancer Lett. 2021 Nov 1;520:201-212. |
Mice (C57BL/6, NRG, NSG) | ID8 (p53−/− BRCA1−/−) HGSC model and HGSC PDX models (DF86, DF149, LP28) | Intravenous (IV) or intraperitoneal (IP) | 30-60 mg/kg | Once per week for 2 weeks | Evaluate the anti-tumor activity of CBL0137 monotherapy in HGSC models, showing significant reduction in ascitic fluid volume and tumor nodules, and prolonged survival of mice. | J Exp Clin Cancer Res. 2022 Dec 21;41(1):355. |
Mice | TH-MYCN+/+ mouse model | Intravenous injection | 60 mg/kg | Every 4 days for 8 doses | Evaluate the inhibitory effect of CBL0137 on neuroblastoma growth | Sci Transl Med. 2015 Nov 4;7(312):312ra176. |
NOD scid IL-2 receptor gamma knockout (NSG) mice | SCLC PDX model | Intraperitoneal (Rova-T), intravenous (CBL0137) | 60 mg/kg (CBL0137), 1.8 mg/kg (Rova-T) | Once weekly (CBL0137), until tumor volume reached ~1200 mm³ | Evaluate the anti-tumor efficacy of CBL0137 combined with Rova-T in SCLC PDX model, results showed significant tumor growth inhibition and prolonged survival | Br J Cancer. 2021 Mar;124(5):893-895. |
BALB/c nude mice | BE(2)-C neuroblastoma xenograft model | Intravenous CBL0137, intraperitoneal PNB | 60 mg/kg CBL0137, 5 mg/kg PNB | CBL0137 every 4 days for 8 doses, PNB for 7 consecutive days | Evaluate the effect of CBL0137 and PNB combination on tumor growth in neuroblastoma xenograft models | Clin Cancer Res. 2021 Aug 1;27(15):4338-4352. |
Nude mice | Orthotopic intracranial xenograft model | Intravenous injection | 70 mg/kg | Every four days for 28 days | Significantly suppressed tumor growth and prolonged survival | Cell Death Dis. 2020 Dec 2;11(12):1029. |
Swiss-Webster mice | Mouse model of chronic HAT | Oral | 80 mg/kg | Once daily for 10 days | Evaluate the efficacy of CBL0137 in a mouse model of chronic HAT, showing a 165-fold reduction in parasite tissue load. | J Med Chem. 2023 Feb 9;66(3):1972-1989. |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT01905228 | Solid Tumors|Glioblastoma | PHASE1 | COMPLETED | 2025-06-19 | Roswell Park Cancer Institute,... More >> Buffalo, New York, 14263, United States|University Hospital of Cleveland, Cleveland, Ohio, 44106, United States|Cleveland Clinic, Cleveland, Ohio, 44195, United States|CTRC at The University of Texas Healh Science Center at San Antonio, San Antonio, Texas, 78229, United States Less << |
NCT02931110 | Hematological Malignancies | PHASE1 | TERMINATED | 2025-10-20 | The Oncology Institute of Hope... More >> & Innovation, Whittier, California, 90603, United States|Claude Sportes, Augusta, Georgia, 30912, United States|Roswell Park Cancer Institute, Buffalo, New York, 14263, United States|University Hospitals Case Medical, Cleveland, Ohio, 44106, United States Less << |
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