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MedKoo Cat#: 407840 | Name: RHPS4 methosulfate
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Description:

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

RHPS4 is a telomerase inhibitor and G-quadruplex ligand. RHPS4 induces anti-proliferative effects in brain tumor cells. RHPS4 potentiates the antitumor activity of camptothecins in preclinical models of solid tumors. RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells.

Chemical Structure

RHPS4 methosulfate
RHPS4 methosulfate
CAS#390362-78-4 (methosulfate)

Theoretical Analysis

MedKoo Cat#: 407840

Name: RHPS4 methosulfate

CAS#: 390362-78-4 (methosulfate)

Chemical Formula: C23H20F2N2O4S

Exact Mass:

Molecular Weight: 458.48

Elemental Analysis: C, 60.25; H, 4.40; F, 8.29; N, 6.11; O, 13.96; S, 6.99

Price and Availability

Size Price Availability Quantity
25mg USD 450.00 2 Weeks
50mg USD 750.00 2 Weeks
100mg USD 1,250.00 2 Weeks
200mg USD 1,950.00 2 Weeks
500mg USD 3,450.00 2 Weeks
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Related CAS #
390362-78-4 (methosulfate) 390362-77-3 (cation)
Synonym
RHPS 4 methosulfate; RHPS-4; RHPS 4; RHPS4.
IUPAC/Chemical Name
3,11-difluoro-6,8,13-trimethyl-8H-quinolino[4,3,2-kl]acridin-13-ium methyl sulfate
InChi Key
VRWGYMXWYZBBGF-UHFFFAOYSA-M
InChi Code
InChI=1S/C22H17F2N2.CH4O4S/c1-12-8-16-15-10-13(23)4-6-18(15)26(3)22-17-11-14(24)5-7-19(17)25(2)20(9-12)21(16)22;1-5-6(2,3)4/h4-11H,1-3H3;1H3,(H,2,3,4)/q+1;/p-1
SMILES Code
C[N+]4=C2C3=C(C=C(C)C=C3C5=C4C=CC(F)=C5)N(C)C1=CC=C(F)C=C12.COS(=O)([O-])=O
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 and water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO and water
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
Instruction
View handling instruction
Biological target:
RHPS4 inhibits the growth of medulloblastoma and glioblastoma cells in vitro. It induces telomere injury and apoptosis, and reduces growth in CG5 breast cancer cell xenografts in mice. RHPS4 sensitizes radiation resistant glioblastoma cell lines to radiation.
In vitro activity:
All cell lines tested in this study were sensitive to RHPS4, but PFSK-1 central nervous system primitive neuroectodermal cells, DAOY medulloblastoma cells and U87 glioblastoma cells exhibited up to 30-fold increased sensitivity compared to KNS42 glioblastoma, C6 glioma and Res196 ependymoma cells. This study supports further research into RHPS4 and alternative G4 ligands as potential anti-cancer agents for brain tumors. Reference: PLoS One. 2014 Jan 15;9(1):e86187. https://pubmed.ncbi.nlm.nih.gov/24454961/
In vivo activity:
Treatment of mice with irinotecan followed by RHPS4 was able to inhibit and delay tumor growth and to increase mouse survival. RHPS4 has a good pharmacodynamic profile. In combination therapy, it produces strong antitumoral activity. Reference: Clin Cancer Res. 2008 Nov 15;14(22):7284-91. https://pubmed.ncbi.nlm.nih.gov/19010844/
Solvent mg/mL mM
Solubility
DMSO 9.2 20.00
Water 4.6 10.00
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 458.48 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. Lagah S, Tan IL, Radhakrishnan P, Hirst RA, Ward JH, O'Callaghan C, Smith SJ, Stevens MF, Grundy RG, Rahman R. RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells. PLoS One. 2014 Jan 15;9(1):e86187. doi: 10.1371/journal.pone.0086187. PMID: 24454961; PMCID: PMC3893285. 2. Cookson JC, Dai F, Smith V, Heald RA, Laughton CA, Stevens MF, Burger AM. Pharmacodynamics of the G-quadruplex-stabilizing telomerase inhibitor 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in vitro: activity in human tumor cells correlates with telomere length and can be enhanced, or antagonized, with cytotoxic agents. Mol Pharmacol. 2005 Dec;68(6):1551-8. doi: 10.1124/mol.105.013300. Epub 2005 Sep 8. PMID: 16150933. 3. Leonetti C, Scarsella M, Riggio G, Rizzo A, Salvati E, D'Incalci M, Staszewsky L, Frapolli R, Stevens MF, Stoppacciaro A, Mottolese M, Antoniani B, Gilson E, Zupi G, Biroccio A. G-quadruplex ligand RHPS4 potentiates the antitumor activity of camptothecins in preclinical models of solid tumors. Clin Cancer Res. 2008 Nov 15;14(22):7284-91. doi: 10.1158/1078-0432.CCR-08-0941. PMID: 19010844. 4. Salvati E, Leonetti C, Rizzo A, Scarsella M, Mottolese M, Galati R, Sperduti I, Stevens MF, D'Incalci M, Blasco M, Chiorino G, Bauwens S, Horard B, Gilson E, Stoppacciaro A, Zupi G, Biroccio A. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. J Clin Invest. 2007 Nov;117(11):3236-47. doi: 10.1172/JCI32461. PMID: 17932567; PMCID: PMC2000812.
In vitro protocol:
1. Lagah S, Tan IL, Radhakrishnan P, Hirst RA, Ward JH, O'Callaghan C, Smith SJ, Stevens MF, Grundy RG, Rahman R. RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells. PLoS One. 2014 Jan 15;9(1):e86187. doi: 10.1371/journal.pone.0086187. PMID: 24454961; PMCID: PMC3893285. 2. Cookson JC, Dai F, Smith V, Heald RA, Laughton CA, Stevens MF, Burger AM. Pharmacodynamics of the G-quadruplex-stabilizing telomerase inhibitor 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in vitro: activity in human tumor cells correlates with telomere length and can be enhanced, or antagonized, with cytotoxic agents. Mol Pharmacol. 2005 Dec;68(6):1551-8. doi: 10.1124/mol.105.013300. Epub 2005 Sep 8. PMID: 16150933.
In vivo protocol:
1. Leonetti C, Scarsella M, Riggio G, Rizzo A, Salvati E, D'Incalci M, Staszewsky L, Frapolli R, Stevens MF, Stoppacciaro A, Mottolese M, Antoniani B, Gilson E, Zupi G, Biroccio A. G-quadruplex ligand RHPS4 potentiates the antitumor activity of camptothecins in preclinical models of solid tumors. Clin Cancer Res. 2008 Nov 15;14(22):7284-91. doi: 10.1158/1078-0432.CCR-08-0941. PMID: 19010844. 2. Salvati E, Leonetti C, Rizzo A, Scarsella M, Mottolese M, Galati R, Sperduti I, Stevens MF, D'Incalci M, Blasco M, Chiorino G, Bauwens S, Horard B, Gilson E, Stoppacciaro A, Zupi G, Biroccio A. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. J Clin Invest. 2007 Nov;117(11):3236-47. doi: 10.1172/JCI32461. PMID: 17932567; PMCID: PMC2000812.
1: Berardinelli F, Siteni S, Tanzarella C, Stevens MF, Sgura A, Antoccia A. The G-quadruplex-stabilising agent RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells. DNA Repair (Amst). 2015 Jan;25:104-15. doi: 10.1016/j.dnarep.2014.10.009. Epub 2014 Nov 5. PubMed PMID: 25467559. 2: Lagah S, Tan IL, Radhakrishnan P, Hirst RA, Ward JH, O'Callaghan C, Smith SJ, Stevens MF, Grundy RG, Rahman R. RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells. PLoS One. 2014 Jan 15;9(1):e86187. doi: 10.1371/journal.pone.0086187. eCollection 2014. PubMed PMID: 24454961; PubMed Central PMCID: PMC3893285. 3: Rizzo A, Iachettini S, Zizza P, Cingolani C, Porru M, Artuso S, Stevens M, Hummersone M, Biroccio A, Salvati E, Leonetti C. Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities. J Exp Clin Cancer Res. 2014 Oct 6;33:81. doi: 10.1186/s13046-014-0081-x. Erratum in: J Exp Clin Cancer Res. 2015;34:9. PubMed PMID: 25288403; PubMed Central PMCID: PMC4193996. 4: Leonetti C, Scarsella M, Riggio G, Rizzo A, Salvati E, D'Incalci M, Staszewsky L, Frapolli R, Stevens MF, Stoppacciaro A, Mottolese M, Antoniani B, Gilson E, Zupi G, Biroccio A. G-quadruplex ligand RHPS4 potentiates the antitumor activity of camptothecins in preclinical models of solid tumors. Clin Cancer Res. 2008 Nov 15;14(22):7284-91. doi: 10.1158/1078-0432.CCR-08-0941. PubMed PMID: 19010844. 5: Leonetti C, Amodei S, D'Angelo C, Rizzo A, Benassi B, Antonelli A, Elli R, Stevens MF, D'Incalci M, Zupi G, Biroccio A. Biological activity of the G-quadruplex ligand RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) is associated with telomere capping alteration. Mol Pharmacol. 2004 Nov;66(5):1138-46. Epub 2004 Aug 10. PubMed PMID: 15304549. 6: Phatak P, Cookson JC, Dai F, Smith V, Gartenhaus RB, Stevens MF, Burger AM. Telomere uncapping by the G-quadruplex ligand RHPS4 inhibits clonogenic tumour cell growth in vitro and in vivo consistent with a cancer stem cell targeting mechanism. Br J Cancer. 2007 Apr 23;96(8):1223-33. Epub 2007 Apr 3. PubMed PMID: 17406367; PubMed Central PMCID: PMC2360152. 7: Johnson LA, Byrne HM, Willis AE, Laughton CA. An integrative biological approach to the analysis of tissue culture data: application to the antitumour agent RHPS4. Integr Biol (Camb). 2011 Aug;3(8):843-9. doi: 10.1039/c1ib00025j. Epub 2011 Jul 19. PubMed PMID: 21773618. 8: Salvati E, Leonetti C, Rizzo A, Scarsella M, Mottolese M, Galati R, Sperduti I, Stevens MF, D'Incalci M, Blasco M, Chiorino G, Bauwens S, Horard B, Gilson E, Stoppacciaro A, Zupi G, Biroccio A. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. J Clin Invest. 2007 Nov;117(11):3236-47. PubMed PMID: 17932567; PubMed Central PMCID: PMC2000812. 9: Cookson JC, Dai F, Smith V, Heald RA, Laughton CA, Stevens MF, Burger AM. Pharmacodynamics of the G-quadruplex-stabilizing telomerase inhibitor 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in vitro: activity in human tumor cells correlates with telomere length and can be enhanced, or antagonized, with cytotoxic agents. Mol Pharmacol. 2005 Dec;68(6):1551-8. Epub 2005 Sep 8. PubMed PMID: 16150933. 10: Rizzo A, Iachettini S, Zizza P, Cingolani C, Porru M, Artuso S, Stevens M, Hummersone M, Biroccio A, Salvati E, Leonetti C. Erratum: identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities. J Exp Clin Cancer Res. 2015 Feb 5;34:9. doi: 10.1186/s13046-014-0101-x. PubMed PMID: 25886908; PubMed Central PMCID: PMC4326507. 11: Rizzo A, Salvati E, Porru M, D'Angelo C, Stevens MF, D'Incalci M, Leonetti C, Gilson E, Zupi G, Biroccio A. Stabilization of quadruplex DNA perturbs telomere replication leading to the activation of an ATR-dependent ATM signaling pathway. Nucleic Acids Res. 2009 Sep;37(16):5353-64. doi: 10.1093/nar/gkp582. Epub 2009 Jul 13. PubMed PMID: 19596811; PubMed Central PMCID: PMC2760797. 12: Shah A, Seedhouse C. Frequency of TP53 Mutations and its Impact on Drug Sensitivity in Acute Myeloid Leukemia? Indian J Clin Biochem. 2012 Apr;27(2):121-6. doi: 10.1007/s12291-012-0203-1. Epub 2012 Mar 24. Retraction in: Indian J Clin Biochem. 2014 Apr;29(2):265. PubMed PMID: 23543587; PubMed Central PMCID: PMC3358364. 13: Hirt BV, Wattis JA, Preston SP, Laughton CA. The effects of a telomere destabilizing agent on cancer cell-cycle dynamics--integrated modelling and experiments. J Theor Biol. 2012 Feb 21;295:9-22. doi: 10.1016/j.jtbi.2011.10.038. Epub 2011 Nov 18. PubMed PMID: 22108242. 14: Gowan SM, Heald R, Stevens MF, Kelland LR. Potent inhibition of telomerase by small-molecule pentacyclic acridines capable of interacting with G-quadruplexes. Mol Pharmacol. 2001 Nov;60(5):981-8. PubMed PMID: 11641426. 15: Kim J, Jones-Hall YL, Wei R, Myers J, Qi Y, Knipp GT, Liu W. Association between hTERT rs2736100 polymorphism and sensitivity to anti-cancer agents. Front Genet. 2013 Aug 26;4:162. doi: 10.3389/fgene.2013.00162. eCollection 2013. PubMed PMID: 23986774; PubMed Central PMCID: PMC3752523. 16: Salvati E, Scarsella M, Porru M, Rizzo A, Iachettini S, Tentori L, Graziani G, D'Incalci M, Stevens MF, Orlandi A, Passeri D, Gilson E, Zupi G, Leonetti C, Biroccio A. PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy. Oncogene. 2010 Nov 25;29(47):6280-93. doi: 10.1038/onc.2010.344. Epub 2010 Aug 30. PubMed PMID: 20802516. 17: Gavathiotis E, Heald RA, Stevens MF, Searle MS. Drug recognition and stabilisation of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat. J Mol Biol. 2003 Nov 14;334(1):25-36. PubMed PMID: 14596797. 18: Iachettini S, Stevens MF, Frigerio M, Hummersone MG, Hutchinson I, Garner TP, Searle MS, Wilson DW, Munde M, Nanjunda R, D'Angelo C, Zizza P, Rizzo A, Cingolani C, De Cicco F, Porru M, D'Incalci M, Leonetti C, Biroccio A, Salvati E. On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts. J Exp Clin Cancer Res. 2013 Sep 19;32:68. doi: 10.1186/1756-9966-32-68. PubMed PMID: 24330541; PubMed Central PMCID: PMC3849007. 19: Husby J, Todd AK, Platts JA, Neidle S. Small-molecule G-quadruplex interactions: Systematic exploration of conformational space using multiple molecular dynamics. Biopolymers. 2013 Dec;99(12):989-1005. doi: 10.1002/bip.22340. PubMed PMID: 23828641. 20: Andrew EJ, Merchan S, Lawless C, Banks AP, Wilkinson DJ, Lydall D. Pentose phosphate pathway function affects tolerance to the G-quadruplex binder TMPyP4. PLoS One. 2013 Jun 12;8(6):e66242. doi: 10.1371/journal.pone.0066242. Print 2013. PubMed PMID: 23776642; PubMed Central PMCID: PMC3680382.