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Chemical Structure| 1197996-80-7 Chemical Structure| 1197996-80-7

Structure of CBL0137
CAS No.: 1197996-80-7

Chemical Structure| 1197996-80-7

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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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Product Details of CBL0137

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
MDL No. :MFCD18071578

Safety of CBL0137

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of CBL0137

epigenetics
DNA
pyroptosis

Isoform Comparison

Biological Activity

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].

In Vitro:

Cell Line
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:

Species
Animal Model
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 <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.97mL

0.59mL

0.30mL

14.86mL

2.97mL

1.49mL

29.72mL

5.94mL

2.97mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

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