Lotamilast (RVT-501)
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MedKoo CAT#: 528909

CAS#: 947620-48-6

Description: RVT-501, also known as E-6005 and lotamilast, is a phosphodiesterase 4 (PDE-4) inhibitor potentially for the treatment of atopic dermatitis.


Chemical Structure

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Lotamilast (RVT-501)
CAS# 947620-48-6

Theoretical Analysis

MedKoo Cat#: 528909
Name: Lotamilast (RVT-501)
CAS#: 947620-48-6
Chemical Formula: C26H24N4O5
Exact Mass: 472.17
Molecular Weight: 472.500
Elemental Analysis: C, 66.09; H, 5.12; N, 11.86; O, 16.93

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3750 Ready to ship
2g USD 6250 2 Weeks
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Synonym: E-6005; E6005; E6005; RVT-501; RVT501; RVT 501; lotamilast;

IUPAC/Chemical Name: methyl 4-((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)carbamoyl)benzoate

InChi Key: BBTFKAOFCSOZMB-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H24N4O5/c1-27-26-29-20-14-22(34-3)21(33-2)13-19(20)23(30-26)17-6-5-7-18(12-17)28-24(31)15-8-10-16(11-9-15)25(32)35-4/h5-14H,1-4H3,(H,28,31)(H,27,29,30)

SMILES Code: O=C(OC)C1=CC=C(C(NC2=CC=CC(C3=C4C=C(OC)C(OC)=CC4=NC(NC)=N3)=C2)=O)C=C1

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:

Biological target: Lotamilast (RVT-501; E6005) is a selective phosphodiesterase 4 (PDE4) inhibitor with an IC50 of 2.8 nM.
In vitro activity: E6005 potently and selectively inhibited human PDE4 activity with an IC₅₀ of 2.8 nM and suppressed the production of various cytokines from human lymphocytes and monocytes with IC₅₀ values ranging from 0.49 to 3.1 nM. Reference: J Pharmacol Exp Ther. 2013 Jul;346(1):105-12. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=23674603
In vivo activity: Topical E6005/RVT-501 ameliorates the dermatitis score of chronic murine dermatitis by repeated application of oxazolone, which is associated with a downregulation of IL-1β and IL-4 gene expression. Mite-induced murine dermatitis is also inhibited by topical E6005/RVT-501. In histology analyses, topical E6005/RVT-501 reduced the epidermal acanthosis both in oxazolone- and mite-induced dermatitis models. Topical application of E6005/RVT-501 does increase and normalize the decreased cAMP levels in murine dermatitis lesions (Table 1). Reference: Expert Opin Investig Drugs. 2017 Dec;26(12):1403-1408. https://www.tandfonline.com/doi/full/10.1080/13543784.2017.1397626

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 52.90

Preparing Stock Solutions

The following data is based on the product molecular weight 472.50 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:
In vitro protocol: 1. Ishii N, Shirato M, Wakita H, Miyazaki K, Takase Y, Asano O, Kusano K, Yamamoto E, Inoue C, Hishinuma I. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12. doi: 10.1124/jpet.113.205542. Epub 2013 May 14. PMID: 23674603. 2. Furue M, Kadono T, Tsuji G, Nakahara T. Topical E6005/RVT-501, a novel phosphodiesterase 4 inhibitor, for the treatment of atopic dermatitis. Expert Opin Investig Drugs. 2017 Dec;26(12):1403-1408. doi: 10.1080/13543784.2017.1397626. Epub 2017 Oct 31. PMID: 29068253.
In vivo protocol: 1. Andoh T, Yoshida T, Kuraishi Y. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61. doi: 10.1111/exd.12377. PMID: 24645735. 2. Furue M, Kadono T, Tsuji G, Nakahara T. Topical E6005/RVT-501, a novel phosphodiesterase 4 inhibitor, for the treatment of atopic dermatitis. Expert Opin Investig Drugs. 2017 Dec;26(12):1403-1408. doi: 10.1080/13543784.2017.1397626. Epub 2017 Oct 31. PMID: 29068253.

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1: Nemoto O, Hayashi N, Kitahara Y, Furue M, Hojo S, Nomoto M, Shima S; Japanese E6005 Study Investigators.. Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: Results from a randomized, vehicle-controlled exploratory trial. J Dermatol. 2016 Aug;43(8):881-7. doi: 10.1111/1346-8138.13231. PubMed PMID: 26703371.

2: Mano Y, Ishii T, Hotta K, Kusano K. Validation of a UPLC-MS/MS method for the simultaneous determination of E6005, a phosphodiesterase 4 inhibitor, and its metabolite in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Aug 15;998-999:31-9. doi: 10.1016/j.jchromb.2015.06.023. PubMed PMID: 26149248.

3: Furue M, Kitahara Y, Akama H, Hojo S, Hayashi N, Nakagawa H; JAPANESE E6005 Study Investigators.. Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial. J Dermatol. 2014 Jul;41(7):577-85. doi: 10.1111/1346-8138.12534. PubMed PMID: 24942594.

4: Ohba F, Nomoto M, Hojo S, Akama H. Safety, tolerability and pharmacokinetics of a novel phosphodiesterase inhibitor, E6005 ointment, in healthy volunteers and in patients with atopic dermatitis. J Dermatolog Treat. 2016;27(3):241-6. doi: 10.3109/09546634.2015.1093587. PubMed PMID: 26581111.

5: Ohba F, Matsuki S, Imayama S, Matsuguma K, Hojo S, Nomoto M, Akama H. Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study. J Dermatolog Treat. 2016 Oct;27(5):467-72. doi: 10.3109/09546634.2016.1157257. PubMed PMID: 27080209.

6: Andoh T, Kuraishi Y. Antipruritic mechanisms of topical E6005, a phosphodiesterase 4 inhibitor: inhibition of responses to proteinase-activated receptor 2 stimulation mediated by increase in intracellular cyclic AMP. J Dermatol Sci. 2014 Dec;76(3):206-13. doi: 10.1016/j.jdermsci.2014.10.005. PubMed PMID: 25458869.

7: Wakita H, Ohkuro M, Ishii N, Hishinuma I, Shirato M. A putative antipruritic mechanism of the phosphodiesterase-4 inhibitor E6005 by attenuating capsaicin-induced depolarization of C-fibre nerves. Exp Dermatol. 2015 Mar;24(3):215-6. doi: 10.1111/exd.12606. PubMed PMID: 25431172.

8: Kubota S, Watanabe M, Shirato M, Okuno T, Higashimoto I, Machida K, Yokomizo T, Inoue H. An inhaled phosphodiesterase 4 inhibitor E6005 suppresses pulmonary inflammation in mice. Eur J Pharmacol. 2015 Dec 5;768:41-8. doi: 10.1016/j.ejphar.2015.10.013. PubMed PMID: 26455478.

9: Ishii N, Shirato M, Wakita H, Miyazaki K, Takase Y, Asano O, Kusano K, Yamamoto E, Inoue C, Hishinuma I. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12. doi: 10.1124/jpet.113.205542. PubMed PMID: 23674603.

10: Andoh T, Yoshida T, Kuraishi Y. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61. doi: 10.1111/exd.12377. PubMed PMID: 24645735.

11: Ishii N, Wakita H, Shirato M. Effect of the phosphodiesterase 4 inhibitor E6005 on nerve growth factor elevation in irritated skin of NC/Nga mice. J Dermatol Sci. 2014 Dec;76(3):263-4. doi: 10.1016/j.jdermsci.2014.09.010. PubMed PMID: 25455141.

12: Leaños-Miranda A, Méndez-Aguilar F, Ramírez-Valenzuela KL, Serrano-Rodríguez M, Berumen-Lechuga G, Molina-Pérez CJ, Isordia-Salas I, Campos-Galicia I. Circulating angiogenic factors are related to the severity of gestational hypertension and preeclampsia, and their adverse outcomes. Medicine (Baltimore). 2017 Jan;96(4):e6005. doi: 10.1097/MD.0000000000006005. PubMed PMID: 28121958; PubMed Central PMCID: PMC5287982.

13: Mano Y, Kita K, Kusano K. Hematocrit-independent recovery is a key for bioanalysis using volumetric absorptive microsampling devices, Mitra™. Bioanalysis. 2015;7(15):1821-9. doi: 10.4155/bio.15.111. PubMed PMID: 26295984.

14: Nakamuta JS, Danoviz ME, Marques FL, dos Santos L, Becker C, Gonçalves GA, Vassallo PF, Schettert IT, Tucci PJ, Krieger JE. Cell therapy attenuates cardiac dysfunction post myocardial infarction: effect of timing, routes of injection and a fibrin scaffold. PLoS One. 2009 Jun 23;4(6):e6005. doi: 10.1371/journal.pone.0006005. PubMed PMID: 19547700; PubMed Central PMCID: PMC2695782.

15: Kuo I I, Fischer B, Vlahov D. Consideration of a North American heroin-assisted clinical trial for the treatment of opiate-dependent individuals. Int J Drug Policy. 2000 Sep 1;11(5):357-370. PubMed PMID: 10967518.