WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406586
CAS#: 896705-16-1
Description: BMH-21 is a potent small molecule DNA intercalator. BMH-21 binds ribosomal DNA and inhibits RNA polymerase I (Pol I) transcription. BMH-21 does not cause phosphorylation of H2AX, a key biomarker activated in DNA damage stress. BMH-21 effects on the nucleolar stress response were independent of major DNA damage associated PI3-kinase pathways, ATM, ATR and DNA-PKcs. BMH-21 is a chemically unique DNA intercalator that has high bioactivity towards Pol I inhibition without activation or dependence of DNA damage stress. The findings also show that interference with DNA and DNA metabolic processes can be exploited therapeutically without causing DNA damage.
MedKoo Cat#: 406586
Name: BMH-21
CAS#: 896705-16-1
Chemical Formula: C21H22N4O2
Exact Mass: 362.1743
Molecular Weight: 362.43
Elemental Analysis: C, 69.59; H, 6.12; N, 15.46; O, 8.83
Synonym: BMH21; BMH 21; BMH-21.
IUPAC/Chemical Name: N-(2-(dimethylamino)ethyl)-12-oxo-11a,12-dihydro-5aH-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide
InChi Key: FSCFXXLAGKOPMP-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H22N4O2/c1-24(2)11-9-22-20(26)16-8-5-10-25-19(16)23-18-13-15-7-4-3-6-14(15)12-17(18)21(25)27/h3-8,10,12-13,17-18H,9,11H2,1-2H3,(H,22,26)
SMILES Code: O=C(C1=CC=CN2C1=NC3C=C(C=CC=C4)C4=CC3C2=O)NCCN(C)C
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | BMH-21 is a DNA intercalator that inhibits RNA polymerase I (Pol I) transcription and possesses anticancer activity. |
| In vitro activity: | To evaluate the inhibitory effect of BMH-21 on SKOV3, Bel-7402 and HeLa cell viability, cells were treated with increasing doses of BMH-21 for 24 h and cell viability was determined by an MTT assay. BMH-21 treatment decreased the viability of SKOV3, Bel-7402 and HeLa cells in a dose-dependent manner (Fig. 1A, E and F). Based on MTT results, we treated SKOV3 cells with increasing doses of BMH-21 (1, 2 and 4 µM) for 24 h. The changes in SKOV3 cell morphology were examined using an inverted optical microscope. The cells treated with BMH-21 became fragmented and round when compared with control cells (Fig. 1B). To examine the distribution of cell cycle progression, the effect of BMH-21 in various cell cycle phases was confirmed using flow cytometry. BMH21 resulted in a marked increase in the percentage of cells blocked at G2/M phase (Fig. 1C and D). These findings indicated that BMH-21 effectively inhibited cancer cell viability and suggested that BMH-21 induced cell death. Reference: Oncol Rep. 2017 Aug; 38(2): 859–865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561869/ |
| In vivo activity: | To further understand the role of BMH-21 in prostate tumorigenesis in another preclinical prostate cancer model, the Hoxb13MYC|Hoxb13-Cre|Ptenfl/fl (BMPC) mouse prostate cancer model in which the development of aggressive tumors is detected at 16 to 20 weeks of age was used The BMPC mice develop castration resistance and lose expression of AR around 20 weeks of age. As observed in Figure 7C, cells isolated from BMPC tumors31 had negligible AR expression. BMPC-1 cells were then treated with BMH-21 for 48 hours. A robust reduction in their growth (Figure 8A) was observed. To explore the potential of BMH-21 to repress tumor growth on these established tumors, treatments were initatied using an intraperitoneal administration of BMH-21 at 50 mg/kg at the age of 20 weeks and followed individual mice until the palpable tumor burden reached a euthanasia endpoint (Figure 8B). There was no statistical difference between the survival of vehicle and BMH-21 treated mice (Figure 8C). However, it was observed that BMH-21 treatment significantly reduced the tumor burden as measured by urogenital block size compared to vehicle control (Figure 8C). Histological analysis of the urogenital block also demonstrated a reduction in invasion compared to vehicle control (Figure 8D and 8E). The findings from this genetic mouse model suggest that BMH-21 may be a potential first-in-class molecule that is able to inhibit prostate tumorigenesis. Reference: Prostate. 2019 Dec; 79(16): 1837–1851. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7025478/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 2.2 | 6.07 |
The following data is based on the product molecular weight 362.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Fu X, Xu L, Qi L, Tian H, Yi D, Yu Y, Liu S, Li S, Xu Y, Wang C. BMH-21 inhibits viability and induces apoptosis by p53dependent nucleolar stress responses in SKOV3 ovarian cancer cells. Oncol Rep. 2017 Aug;38(2):859-865. doi: 10.3892/or.2017.5750. Epub 2017 Jun 23. PMID: 28656213; PMCID: PMC5561869. 2. Colis L, Peltonen K, Sirajuddin P, Liu H, Sanders S, Ernst G, Barrow JC, Laiho M. DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response. Oncotarget. 2014 Jun 30;5(12):4361-9. doi: 10.18632/oncotarget.2020. PMID: 24952786; PMCID: PMC4147329 3. Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell. 2014 Jan 13;25(1):77-90. doi: 10.1016/j.ccr.2013.12.009. PMID: 24434211; PMCID: PMC3930145. 4. Low JY, Sirajuddin P, Moubarek M, Agarwal S, Rege A, Guner G, Liu H, Yang Z, De Marzo AM, Bieberich C, Laiho M. Effective targeting of RNA polymerase I in treatment-resistant prostate cancer. Prostate. 2019 Dec;79(16):1837-1851. doi: 10.1002/pros.23909. Epub 2019 Sep 16. PMID: 31524299; PMCID: PMC7025478. |
| In vitro protocol: | 1. Fu X, Xu L, Qi L, Tian H, Yi D, Yu Y, Liu S, Li S, Xu Y, Wang C. BMH-21 inhibits viability and induces apoptosis by p53dependent nucleolar stress responses in SKOV3 ovarian cancer cells. Oncol Rep. 2017 Aug;38(2):859-865. doi: 10.3892/or.2017.5750. Epub 2017 Jun 23. PMID: 28656213; PMCID: PMC5561869. 2. Colis L, Peltonen K, Sirajuddin P, Liu H, Sanders S, Ernst G, Barrow JC, Laiho M. DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response. Oncotarget. 2014 Jun 30;5(12):4361-9. doi: 10.18632/oncotarget.2020. PMID: 24952786; PMCID: PMC4147329 |
| In vivo protocol: | 1. Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell. 2014 Jan 13;25(1):77-90. doi: 10.1016/j.ccr.2013.12.009. PMID: 24434211; PMCID: PMC3930145. 2. Low JY, Sirajuddin P, Moubarek M, Agarwal S, Rege A, Guner G, Liu H, Yang Z, De Marzo AM, Bieberich C, Laiho M. Effective targeting of RNA polymerase I in treatment-resistant prostate cancer. Prostate. 2019 Dec;79(16):1837-1851. doi: 10.1002/pros.23909. Epub 2019 Sep 16. PMID: 31524299; PMCID: PMC7025478. |
1: Peltonen K, Colis L, Liu H, Jäämaa S, Zhang Z, Af Hällström T, Moore HM, Sirajuddin P, Laiho M. Small Molecule BMH-Compounds That Inhibit RNA Polymerase I and Cause Nucleolar Stress. Mol Cancer Ther. 2014 Nov;13(11):2537-46. doi: 10.1158/1535-7163.MCT-14-0256. Epub 2014 Oct 2. PubMed PMID: 25277384; PubMed Central PMCID: PMC4221476.
2: Colis L, Peltonen K, Sirajuddin P, Liu H, Sanders S, Ernst G, Barrow JC, Laiho M. DNA intercalator BMH-21 inhibits RNA polymerase I independent of DNA damage response. Oncotarget. 2014 Jun 30;5(12):4361-9. PubMed PMID: 24952786; PubMed Central PMCID: PMC4147329.
3: Colis L, Ernst G, Sanders S, Liu H, Sirajuddin P, Peltonen K, DePasquale M, Barrow JC, Laiho M. Design, synthesis, and structure-activity relationships of pyridoquinazolinecarboxamides as RNA polymerase I inhibitors. J Med Chem. 2014 Jun 12;57(11):4950-61. doi: 10.1021/jm5004842. Epub 2014 May 30. PubMed PMID: 24847734; PubMed Central PMCID: PMC4059246.
4: Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell. 2014 Jan 13;25(1):77-90. doi: 10.1016/j.ccr.2013.12.009. PubMed PMID: 24434211; PubMed Central PMCID: PMC3930145.
