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MedKoo Cat#: 510322 | Name: RG3039
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Description:

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

RG3039, also known as PF-06687859, is a potent DcpS inhibitor. DcpS is a therapeutic target for spinal muscular atrophy. Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene which produces an essential protein known as SMN. RG3039 improves motor function in SMA mice. RG3039 also showed activity to improve survival, function and motor unit pathologies in two SMA mouse models.

Chemical Structure

RG3039
RG3039
CAS#1005504-62-0

Theoretical Analysis

MedKoo Cat#: 510322

Name: RG3039

CAS#: 1005504-62-0

Chemical Formula: C21H23Cl2N5O

Exact Mass: 431.1280

Molecular Weight: 432.35

Elemental Analysis: C, 58.34; H, 5.36; Cl, 16.40; N, 16.20; O, 3.70

Price and Availability

Size Price Availability Quantity
5mg 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 750.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 5,250.00 Ready to ship
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Related CAS #
No Data
Synonym
RG3039; RG 3039; RG-3039; PF06687859; PF 06687859; PF-06687859
IUPAC/Chemical Name
5-((1-(2,6-dichlorobenzyl)piperidin-4-yl)methoxy)quinazoline-2,4-diamine
InChi Key
SRIYKPCSVUEGET-UHFFFAOYSA-N
InChi Code
InChI=1S/C21H23Cl2N5O.2ClH/c22-15-3-1-4-16(23)14(15)11-28-9-7-13(8-10-28)12-29-18-6-2-5-17-19(18)20(24)27-21(25)26-17;;/h1-6,13H,7-12H2,(H4,24,25,26,27);2*1H
SMILES Code
NC1=NC(N)=C2C(OCC3CCN(CC4=C(Cl)C=CC=C4Cl)CC3)=CC=CC2=N1
Appearance
White to off- white 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
2934.99.03.00
More Info
        
Biological target:
RG3039 (PF-06687859) is a DcpS inhibitor with an IC50 of 0.069 nM.
In vitro activity:
The anti-leukemia effects of RG3039 were assessed by treating 4 human AML (acute myeloid leukemia) lines with RG3039 for 11 days and generating growth curves. RG3039 had dose-dependent anti-proliferative effects, although compound sensitivity varied among lines (Figure 2I). The effects of RG3039 on the cell cycle were also assessed via a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. While EdU was efficiently incorporated into DMSO-treated control cells, EdU incorporation was significantly decreased in RG3039-treated cells, and the proportion of cells in S phase was extremely low in treated versus untreated cells (Figures 2J and 2K). RG3039-treated cells also underwent apoptosis after 72 hr of drug treatment, as revealed by Annexin V stain (Figure 2L). Importantly, observed anti-leukemic effects of RG3039 were caused via TP53-independent mechanisms, as CALM/AF10 and MLL/AF9 AML cells whose TP53 function was abrogated by CRISPR-Cas9-mediated Trp53 knockout were also sensitive to the compound (Figure S3E). Reference: Cancer Cell. 2018 Mar 12;33(3):386-400.e5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849534/
In vivo activity:
Taiwanese hemizygous SMA mice, (SMN2)2Hungtg/0;Smntm1Hung/tm1Hung, here termed 5058 Hemi SMA mice, were used to gain insight into the therapeutic potential of RG3039. The maximum survival of untreated 5058 Hemi SMA mice is 12 days, with an average and median survival of 9 and 10 days, respectively, and clear symptom manifestations starting at P4. Starting at P4, mice were treated qd by oral gavage with RG3039 (20 mg/kg) or vehicle (water). The mice were followed for survival, weight and righting reflex (Supplementary Material, Fig. S2). RG3039-treated SMA mice (n = 20) had a median survival that was 38% greater than vehicle-treated SMA mice (n = 19) (Supplementary Material, Fig. S2A; χ2 = 9.210, P = 0.0024). Furthermore, when placed on their back, RG3039-treated SMA mice were able to right within ∼10–14 s until P11. This differentiated RG3039-treated 5058 Hemi SMA mice from vehicle-treated SMA mice where the later progressed from ∼13 ± 3 s at P6 to 41 ± 13 s at P10 (Supplementary Material, Fig. S2C). These results suggest that RG3039 is able to slow disease progression in 5058 Hemi SMA mice even when the drug is administered well after symptoms have emerged. Reference: Hum Mol Genet. 2013 Oct 15;22(20):4084-101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781638/
Solvent mg/mL mM
Solubility
DMSO 2.0 4.60
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 432.35 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.

Recalculate based on batch purity %
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. Yamauchi T, Masuda T, Canver MC, Seiler M, Semba Y, Shboul M, Al-Raqad M, Maeda M, Schoonenberg VAC, Cole MA, Macias-Trevino C, Ishikawa Y, Yao Q, Nakano M, Arai F, Orkin SH, Reversade B, Buonamici S, Pinello L, Akashi K, Bauer DE, Maeda T. Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell. 2018 Mar 12;33(3):386-400.e5. doi: 10.1016/j.ccell.2018.01.012. Epub 2018 Feb 22. PMID: 29478914; PMCID: PMC5849534. 2. Gogliotti RG, Cardona H, Singh J, Bail S, Emery C, Kuntz N, Jorgensen M, Durens M, Xia B, Barlow C, Heier CR, Plasterer HL, Jacques V, Kiledjian M, Jarecki J, Rusche J, DiDonato CJ. The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Hum Mol Genet. 2013 Oct 15;22(20):4084-101. doi: 10.1093/hmg/ddt258. Epub 2013 Jun 4. PMID: 23736298; PMCID: PMC3781638.
In vitro protocol:
1. Yamauchi T, Masuda T, Canver MC, Seiler M, Semba Y, Shboul M, Al-Raqad M, Maeda M, Schoonenberg VAC, Cole MA, Macias-Trevino C, Ishikawa Y, Yao Q, Nakano M, Arai F, Orkin SH, Reversade B, Buonamici S, Pinello L, Akashi K, Bauer DE, Maeda T. Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell. 2018 Mar 12;33(3):386-400.e5. doi: 10.1016/j.ccell.2018.01.012. Epub 2018 Feb 22. PMID: 29478914; PMCID: PMC5849534.
In vivo protocol:
1. Gogliotti RG, Cardona H, Singh J, Bail S, Emery C, Kuntz N, Jorgensen M, Durens M, Xia B, Barlow C, Heier CR, Plasterer HL, Jacques V, Kiledjian M, Jarecki J, Rusche J, DiDonato CJ. The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Hum Mol Genet. 2013 Oct 15;22(20):4084-101. doi: 10.1093/hmg/ddt258. Epub 2013 Jun 4. PMID: 23736298; PMCID: PMC3781638.
1: Jin B, Yang L, Ye Q, Pan J. Ferroptosis induced by DCPS depletion diminishes hepatic metastasis in uveal melanoma. Biochem Pharmacol. 2023 Jul;213:115625. doi: 10.1016/j.bcp.2023.115625. Epub 2023 May 26. PMID: 37245534. 2: Swartzel JC, Bond MJ, Pintado-Urbanc AP, Daftary M, Krone MW, Douglas T, Carder EJ, Zimmer JT, Maeda T, Simon MD, Crews CM. Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC. ACS Chem Biol. 2022 Jul 15;17(7):1789-1798. doi: 10.1021/acschembio.2c00145. Epub 2022 Jun 24. PMID: 35749470; PMCID: PMC10367122. 3: Yamauchi T. [Exploration of novel therapeutic targets in acute myeloid leukemia via genome-wide CRISPR screening]. Rinsho Ketsueki. 2019;60(7):810-817. Japanese. doi: 10.11406/rinketsu.60.810. PMID: 31391371. 4: Yamauchi T, Masuda T, Canver MC, Seiler M, Semba Y, Shboul M, Al-Raqad M, Maeda M, Schoonenberg VAC, Cole MA, Macias-Trevino C, Ishikawa Y, Yao Q, Nakano M, Arai F, Orkin SH, Reversade B, Buonamici S, Pinello L, Akashi K, Bauer DE, Maeda T. Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell. 2018 Mar 12;33(3):386-400.e5. doi: 10.1016/j.ccell.2018.01.012. Epub 2018 Feb 22. PMID: 29478914; PMCID: PMC5849534. 5: Gentillon C, Connell AJ, Kirk RW, Butchbach MER. The effects of C5-substituted 2,4-diaminoquinazolines on selected transcript expression in spinal muscular atrophy cells. PLoS One. 2017 Jun 29;12(6):e0180657. doi: 10.1371/journal.pone.0180657. PMID: 28662219; PMCID: PMC5491266. 6: Gopalsamy A, Narayanan A, Liu S, Parikh MD, Kyne RE Jr, Fadeyi O, Tones MA, Cherry JJ, Nabhan JF, LaRosa G, Petersen DN, Menard C, Foley TL, Noell S, Ren Y, Loria PM, Maglich-Goodwin J, Rong H, Jones LH. Design of Potent mRNA Decapping Scavenger Enzyme (DcpS) Inhibitors with Improved Physicochemical Properties To Investigate the Mechanism of Therapeutic Benefit in Spinal Muscular Atrophy (SMA). J Med Chem. 2017 Apr 13;60(7):3094-3108. doi: 10.1021/acs.jmedchem.7b00124. Epub 2017 Mar 16. PMID: 28257199. 7: Calder AN, Androphy EJ, Hodgetts KJ. Small Molecules in Development for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2016 Nov 23;59(22):10067-10083. doi: 10.1021/acs.jmedchem.6b00670. Epub 2016 Aug 16. PMID: 27490705; PMCID: PMC5744254. 8: Zhou M, Bail S, Plasterer HL, Rusche J, Kiledjian M. DcpS is a transcript- specific modulator of RNA in mammalian cells. RNA. 2015 Jul;21(7):1306-12. doi: 10.1261/rna.051573.115. Epub 2015 May 22. PMID: 26001796; PMCID: PMC4478349. 9: Gogliotti RG, Cardona H, Singh J, Bail S, Emery C, Kuntz N, Jorgensen M, Durens M, Xia B, Barlow C, Heier CR, Plasterer HL, Jacques V, Kiledjian M, Jarecki J, Rusche J, DiDonato CJ. The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Hum Mol Genet. 2013 Oct 15;22(20):4084-101. doi: 10.1093/hmg/ddt258. Epub 2013 Jun 4. PMID: 23736298; PMCID: PMC3781638. 10: Van Meerbeke JP, Gibbs RM, Plasterer HL, Miao W, Feng Z, Lin MY, Rucki AA, Wee CD, Xia B, Sharma S, Jacques V, Li DK, Pellizzoni L, Rusche JR, Ko CP, Sumner CJ. The DcpS inhibitor RG3039 improves motor function in SMA mice. Hum Mol Genet. 2013 Oct 15;22(20):4074-83. doi: 10.1093/hmg/ddt257. Epub 2013 May 31. PMID: 23727836; PMCID: PMC3781637.