Madrasin | CAS#374913-63-0 | RNA splicing inhibitor

MedKoo Cat#: 326823 | Name: Madrasin

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Madrasin

CAS#374913-63-0

Theoretical Analysis

MedKoo Cat#: 326823

Name: Madrasin

CAS#: 374913-63-0

Chemical Formula: C16H17N5O2

Exact Mass: 311.1382

Molecular Weight: 311.35

Elemental Analysis: C, 61.72; H, 5.50; N, 22.49; O, 10.28

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 850.00	Ready to ship
500mg	USD 1,450.00	Ready to ship
1g	USD 2,450.00	Ready to ship
2g	USD 3,750.00	Ready to ship
5g	USD 6,950.00	2 weeks

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Related CAS #

No Data

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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T05K28

QC Data

View QC data: current batch, Lot#A8T05K28

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	1.5	4.82

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 311.35 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:

In vivo protocol:

TBD

1: Tellier M, Ansa G, Murphy S. Isoginkgetin and Madrasin are poor splicing inhibitors. PLoS One. 2024 Oct 21;19(10):e0310519. doi: 10.1371/journal.pone.0310519. PMID: 39432454; PMCID: PMC11493277. 2: Utomo B, Rimayanti R, Triana IN, Fadholly A. Melanocortin-4 receptor and leptin as genes for the selection of superior Madrasin cattle. Vet World. 2021 Dec;14(12):3224-3228. doi: 10.14202/vetworld.2021.3224-3228. Epub 2021 Dec 31. PMID: 35153416; PMCID: PMC8829405. 3: Angel M, Fleshler E, Atrash MK, Kinor N, Benichou JIC, Shav-Tal Y. Nuclear RNA-related processes modulate the assembly of cytoplasmic RNA granules. Nucleic Acids Res. 2024 May 22;52(9):5356-5375. doi: 10.1093/nar/gkae119. PMID: 38366783; PMCID: PMC11109975. 4: Utomo B, Putranto ED, Fadholly A. Profile of follicle-stimulating hormone and polymorphism of follicle-stimulating hormone receptor in Madrasin cattle with ovarian hypofunction. Vet World. 2020 May;13(5):879-883. doi: 10.14202/vetworld.2020.879-883. Epub 2020 May 11. PMID: 32636582; PMCID: PMC7311873. 5: 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. doi: 10.1074/jbc.A114.590976. PMID: 25281741; PMCID: PMC4263873. 6: Parkhitko AA, Singh A, Hsieh S, Hu Y, Binari R, Lord CJ, Hannenhalli S, Ryan CJ, Perrimon N. Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells. PLoS Genet. 2021 Feb 16;17(2):e1009354. doi: 10.1371/journal.pgen.1009354. PMID: 33591981; PMCID: PMC7909629. 7: 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.