Synonym
Petesicatib; RG-7625; RG 7625; RG7625; RO-5459072; RO 5459072; RO5459072;
IUPAC/Chemical Name
(2S,4R)-N-(1-cyanocyclopropyl)-4-((4-(1-methyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)phenyl)sulfonyl)-1-(1-(trifluoromethyl)cyclopropane-1-carbonyl)pyrrolidine-2-carboxamide
InChi Key
KXAAIORSMACJSI-AEFFLSMTSA-N
InChi Code
InChI=1S/C25H23F6N5O4S/c1-35-11-15(10-33-35)14-2-3-19(17(8-14)24(26,27)28)41(39,40)16-9-18(20(37)34-22(13-32)4-5-22)36(12-16)21(38)23(6-7-23)25(29,30)31/h2-3,8,10-11,16,18H,4-7,9,12H2,1H3,(H,34,37)/t16-,18+/m1/s1
SMILES Code
O=C(N1[C@H](C(NC2(C#N)CC2)=O)C[C@@H](S(=O)(C3=CC=C(C4=CN(C)N=C4)C=C3C(F)(F)F)=O)C1)C5(C(F)(F)F)CC5
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:
Petesicatib is a cathepsin S inhibitor, used in research of immune diseases.
In vitro activity:
RO5459072 significantly diminished specific T cell responses in a dose-dependent manner. Of note, in PBMC cultures (supernatants derived from 48 h ELISPOT assays), RO5459072 significantly diminished TNF-α and IL-10 levels induced by SS-A/SS-B, whereas no suppression was observed for IL-6 and IL-1β, respectively (Fig. 4b). As for IL-6, it is noteworthy that SEB-induced IL-6 levels were significantly reduced by RO5459072, whereas those induced by SS-A and SS-B were not.
Reference: Arthritis Res Ther. 2019 Jul 18;21(1):175. https://pubmed.ncbi.nlm.nih.gov/31319889/
In vivo activity:
Dosing of monkeys with RO5459072 resulted in an intracellular Lip10 accumulation in B cells in the blood of all six animals in vivo, as measured by the flow cytometry assay (Figure 5B). Taken together, these results establish that all monkeys dosed with RO5459072 were responsive to the inhibitor, confirming that cathepsin S inhibitor reached its intended target after oral administration.
Reference: Front Immunol. 2017 Jul 17;8:806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512459/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
125.0 |
207.11 |
|
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
603.54
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. Hargreaves P, Daoudlarian D, Theron M, Kolb FA, Manchester Young M, Reis B, Tiaden A, Bannert B, Kyburz D, Manigold T. Differential effects of specific cathepsin S inhibition in biocompartments from patients with primary Sjögren syndrome. Arthritis Res Ther. 2019 Jul 18;21(1):175. doi: 10.1186/s13075-019-1955-2. PMID: 31319889; PMCID: PMC6637481.
2. Theron M, Bentley D, Nagel S, Manchester M, Gerg M, Schindler T, Silva A, Ecabert B, Teixeira P, Perret C, Reis B. Pharmacodynamic Monitoring of RO5459072, a Small Molecule Inhibitor of Cathepsin S. Front Immunol. 2017 Jul 17;8:806. doi: 10.3389/fimmu.2017.00806. PMID: 28769925; PMCID: PMC5512459.
3. Tato M, Kumar SV, Liu Y, Mulay SR, Moll S, Popper B, Eberhard JN, Thomasova D, Rufer AC, Gruner S, Haap W, Hartmann G, Anders HJ. Cathepsin S inhibition combines control of systemic and peripheral pathomechanisms of autoimmune tissue injury. Sci Rep. 2017 Jun 5;7(1):2775. doi: 10.1038/s41598-017-01894-y. PMID: 28584258; PMCID: PMC5459853.
In vitro protocol:
1. Hargreaves P, Daoudlarian D, Theron M, Kolb FA, Manchester Young M, Reis B, Tiaden A, Bannert B, Kyburz D, Manigold T. Differential effects of specific cathepsin S inhibition in biocompartments from patients with primary Sjögren syndrome. Arthritis Res Ther. 2019 Jul 18;21(1):175. doi: 10.1186/s13075-019-1955-2. PMID: 31319889; PMCID: PMC6637481.
2. Theron M, Bentley D, Nagel S, Manchester M, Gerg M, Schindler T, Silva A, Ecabert B, Teixeira P, Perret C, Reis B. Pharmacodynamic Monitoring of RO5459072, a Small Molecule Inhibitor of Cathepsin S. Front Immunol. 2017 Jul 17;8:806. doi: 10.3389/fimmu.2017.00806. PMID: 28769925; PMCID: PMC5512459.
In vivo protocol:
1. Theron M, Bentley D, Nagel S, Manchester M, Gerg M, Schindler T, Silva A, Ecabert B, Teixeira P, Perret C, Reis B. Pharmacodynamic Monitoring of RO5459072, a Small Molecule Inhibitor of Cathepsin S. Front Immunol. 2017 Jul 17;8:806. doi: 10.3389/fimmu.2017.00806. PMID: 28769925; PMCID: PMC5512459.
2. Tato M, Kumar SV, Liu Y, Mulay SR, Moll S, Popper B, Eberhard JN, Thomasova D, Rufer AC, Gruner S, Haap W, Hartmann G, Anders HJ. Cathepsin S inhibition combines control of systemic and peripheral pathomechanisms of autoimmune tissue injury. Sci Rep. 2017 Jun 5;7(1):2775. doi: 10.1038/s41598-017-01894-y. PMID: 28584258; PMCID: PMC5459853.
1: Kratochwil NA, Stillhart C, Diack C, Nagel S, Al Kotbi N, Frey N. Population pharmacokinetic analysis of RO5459072, a low water-soluble drug exhibiting complex food-drug interactions. Br J Clin Pharmacol. 2021 Sep;87(9):3550-3560. doi: 10.1111/bcp.14771. Epub 2021 Mar 10. PMID: 33576513; PMCID: PMC8451882.
2: Mavragani CP, Moutsopoulos HM. Sjögren's syndrome: Old and new therapeutic targets. J Autoimmun. 2020 Jun;110:102364. doi: 10.1016/j.jaut.2019.102364. Epub 2019 Dec 9. PMID: 31831255.
3: Hargreaves P, Daoudlarian D, Theron M, Kolb FA, Manchester Young M, Reis B, Tiaden A, Bannert B, Kyburz D, Manigold T. Differential effects of specific cathepsin S inhibition in biocompartments from patients with primary Sjögren syndrome. Arthritis Res Ther. 2019 Jul 18;21(1):175. doi: 10.1186/s13075-019-1955-2. PMID: 31319889; PMCID: PMC6637481.
4: Wu, W. F., Lin, J. H., Xiao, J. C., Cao, Y. C., & Ma, Y. (2021). Recent advances in the synthesis of CF3‐or HCF2‐substituted cyclopropanes. Asian Journal of Organic Chemistry, 10(3), 485-495.
Qi, X., Huang, Q., Wang, S., Qiu, L., Chen, X., Ouyang, K., & Chen, Y. (2023). Identification of the shared mechanisms and common biomarkers between Sjögren’s syndrome and atherosclerosis using integrated bioinformatics analysis. Frontiers in Medicine, 10, 1185303.
