WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 326823
CAS#: 374913-63-0
Description: Madrasin is a potent and cell penetrant splicing inhibitor that interferes with the early stages of spliceosome assembly. Madrasin stalls spliceosome assembly at the A complex.
MedKoo Cat#: 326823
Name: Madrasin
CAS#: 374913-63-0
Chemical Formula: C16H17N5O2
Exact Mass: 311.1382
Molecular Weight: 311.345
Elemental Analysis: C, 61.72; H, 5.50; N, 22.49; O, 10.28
Synonym: DDD00107587; Madrasin. RNA splicing inhibitor
IUPAC/Chemical Name: 2-((7-Methoxy-4-methylquinazolin-2-yl)amino)-5,6-dimethylpyrimidin-4(3H)-one
InChi Key: QQJIYKXTEMDJFM-UHFFFAOYSA-N
InChi Code: InChI=1S/C16H17N5O2/c1-8-9(2)17-16(20-14(8)22)21-15-18-10(3)12-6-5-11(23-4)7-13(12)19-15/h5-7H,1-4H3,(H2,17,18,19,20,21,22)
SMILES Code: O=C1NC(NC2=NC(C)=C3C=CC(OC)=CC3=N2)=NC(C)=C1C
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
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: | Madrasin (DDD00107587) is a pre-mRNA splicing inhibitor that prevents formation of both splicing intermediates and products in vitro and interferes with one or more early steps in the pathway of spliceosome assembly. |
| In vitro activity: | To further determine the outcome of splicing defects in POLR2A, HeLa cells were treated with splicing inhibitor madrasin. RT-PCR and western blot revealed that POLR2A expression was down-regulated at RNA and protein levels (Figure3A–D). The inhibitory effect of madrasin on splicing was verified by RT-PCR as the treatment led to substantial increase of unspliced transcripts (Figure3E3E and F). Consistently, IF staining also supported that madrasin treatment resulted in POLR2A down-regulation (Figure3G). In addition, nascent RNA was markedly decreased after madrasin treatment by EU incorporation assay (Figure3H).Similarly, the expression of POLR2A in 293T or MDA-MB-231 cells was decreased at both RNA and protein levels when treated with madrasin (Supplementary Figure S7). These data together supported that splicing defects in POLR2A induced by XAB2 depletion was the major mechanism for decreased expression of POLR2A at RNA level. Reference: Nucleic Acids Res. 2019 Sep 5; 47(15): 8239–8254. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735682/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 1.5 | 4.82 |
The following data is based on the product molecular weight 311.345 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. Hou S, Qu D, Li Y, Zhu B, Liang D, Wei X, Tang W, Zhang Q, Hao J, Guo W, Wang W, Zhao S, Wang Q, Azam S, Khan M, Zhao H, Zhang L, Lei H. XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence. Nucleic Acids Res. 2019 Sep 5;47(15):8239-8254. doi: 10.1093/nar/gkz532. PMID: 31216022; PMCID: PMC6735682. 2. Pawellek A, McElroy S, Samatov T, Mitchell L, Woodland A, Ryder U, Gray D, Lührmann R, Lamond AI. Identification of small molecule inhibitors of pre-mRNA splicing. J Biol Chem. 2014 Dec 12;289(50):34683-98. doi: 10.1074/jbc.M114.590976. Epub 2014 Oct 3. Erratum in: J Biol Chem. 2015 Mar 6;290(10):6005. PMID: 25281741; PMCID: PMC4263873. |
| In vitro protocol: | 1. Hou S, Qu D, Li Y, Zhu B, Liang D, Wei X, Tang W, Zhang Q, Hao J, Guo W, Wang W, Zhao S, Wang Q, Azam S, Khan M, Zhao H, Zhang L, Lei H. XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence. Nucleic Acids Res. 2019 Sep 5;47(15):8239-8254. doi: 10.1093/nar/gkz532. PMID: 31216022; PMCID: PMC6735682. 2. Pawellek A, McElroy S, Samatov T, Mitchell L, Woodland A, Ryder U, Gray D, Lührmann R, Lamond AI. Identification of small molecule inhibitors of pre-mRNA splicing. J Biol Chem. 2014 Dec 12;289(50):34683-98. doi: 10.1074/jbc.M114.590976. Epub 2014 Oct 3. Erratum in: J Biol Chem. 2015 Mar 6;290(10):6005. PMID: 25281741; PMCID: PMC4263873. |
| In vivo protocol: | TBD |
