Roflumilast | Daxas | Daliresp | CAS#162401-32-3 | PDE-4 inhibitor

MedKoo Cat#: 300320 | Name: Roflumilast

Description:

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

Roflumilast (also known as Daxas and Daliresp) acts as a selective, long-acting inhibitor of PDE-4. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs. In June 2010, Daxas was approved in the EU for severe COPD associated with chronic bronchitis. In March 2011, Daliresp gained FDA approval in the US for reducing COPD exacerbations.

Chemical Structure

Roflumilast

CAS#162401-32-3

Theoretical Analysis

MedKoo Cat#: 300320

Name: Roflumilast

CAS#: 162401-32-3

Chemical Formula: C17H14Cl2F2N2O3

Exact Mass: 402.0350

Molecular Weight: 403.21

Elemental Analysis: C, 50.64; H, 3.50; Cl, 17.58; F, 9.42; N, 6.95; O, 11.90

Price and Availability

Size	Price	Availability
250mg	USD 250.00	2 Weeks
500mg	USD 450.00	2 Weeks
1g	USD 750.00	2 Weeks
2g	USD 1,350.00	2 Weeks
5g	USD 2,450.00	2 Weeks

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Related CAS #

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Synonym

BY217; BY-217; BY 217; B 9302-107; B9302-107; B-9302-107; BYK 20869; BYK-20869; BYK20869; Daxas; Daliresp

IUPAC/Chemical Name

3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide

InChi Key

MNDBXUUTURYVHR-UHFFFAOYSA-N

InChi Code

InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)

SMILES Code

O=C(NC1=C(Cl)C=NC=C1Cl)C2=CC=C(OC(F)F)C(OCC3CC3)=C2

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 ethanol

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

Instruction

View handling instruction

Biological target:

Roflumilast inhibits LTB4 synthesis in human neutrophil with IC50 of 2 nM. Roflumilast inhibits fMLP-stimulated ROS formation as luminol-enhanced CL in human neutrophils or eosinophils with IC35 of 4 nM, and 7 nM, repectively. Roflumilast inhibits LPS-stimulated TNF-α synthesis in monocytes with IC40 of 21 nM. Roflumilast inhibits TNF-α synthesis in monocyte-derived dendritic cells with IC20 of 5 nM. Rolfumilast inhibits anti-CD3 and anti-CD28 antibody-stimulated proliferation of CD4+ T cells with IC30 of 7 nM. Rolfumilast inhibits anti-CD3 and anti-CD28 antibody-stimulated synthesis of IL-2, IL-4, IL-5, and IFN-v in CD4+ T cells with IC20 of 1 nM, IC30 of 7 nM, IC25 of 13 nM, and IC35 of 8 nM, respectively.

In vitro activity:

In the PC3 cell line, roflumilast reversed cisplatin (CIS)-induced abnormalities in sperm characteristics, normalized serum testosterone level, ameliorated CIS-induced alterations in testicular and epidydimal weights, and restored normal testicular structure. Roflumilast increased intracellular cAMP levels, PKA, and HO-1 activities; Nrf2, NQO-1 and HO-1 gene expression; improved testicular oxidative stress parameters and inflammatory mediators; and reduced the proapoptotic proteins, caspase-3, Bax and increased Bcl-2. Reference: Food Chem Toxicol. 2021 May;151:112133. https://pubmed.ncbi.nlm.nih.gov/33757793/

In vivo activity:

This study revealed that roflumilast exerted neuroprotective effects in rotenone-induced neurotoxicity in a model of Parkinson's disease in rats. Rats treated with roflumilast showed an improvement in motor activity and coordination and preservation of dopaminergic neurons in the striatum. Roflumilast increased cAMP level and activated the PI3K/AKT axis via stimulation of CREB/BDNF/TrkB and SIRT1/PTP1B/IGF1 signaling cascades. Roflumilast caused an upsurge in mTOR and Nrf2, halted GSK-3β and NF-ĸB, and suppressed FoxO1 and caspase-3. Reference: Inflammopharmacology. 2023 Aug 4. https://pubmed.ncbi.nlm.nih.gov/37541971/

	Solvent	mg/mL	mM
Solubility
	DMSO	81.0	200.89
	Ethanol	15.0	37.20

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 403.21 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. Abdel-Wahab BA, Walbi IA, Albarqi HA, Ali FEM, Hassanein EHM. Roflumilast protects from cisplatin-induced testicular toxicity in male rats and enhances its cytotoxicity in prostate cancer cell line. Role of NF-κB-p65, cAMP/PKA and Nrf2/HO-1, NQO1 signaling. Food Chem Toxicol. 2021 May;151:112133. doi: 10.1016/j.fct.2021.112133. Epub 2021 Mar 20. PMID: 33757793. 2. Gong S, Chen Y, Meng F, Zhang Y, Li C, Zhang G, Huan W, Wu F. Roflumilast enhances cisplatin-sensitivity and reverses cisplatin-resistance of ovarian cancer cells via cAMP/PKA/CREB-FtMt signalling axis. Cell Prolif. 2018 Oct;51(5):e12474. doi: 10.1111/cpr.12474. Epub 2018 Aug 2. PMID: 30069985; PMCID: PMC6528923. 3. Farid HA, Sayed RH, El-Shamarka ME, Abdel-Salam OME, El Sayed NS. PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson's disease in rats. Inflammopharmacology. 2023 Aug 4. doi: 10.1007/s10787-023-01305-x. Epub ahead of print. PMID: 37541971. 4. Patel P, Patel S, Chudasama P, Soni S, Raval M. Roflumilast ameliorates diabetic nephropathy in rats through down-regulation of JAK/STAT signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 15. doi: 10.1007/s00210-023-02535-0. Epub ahead of print. PMID: 37318524.

In vitro protocol:

In vivo protocol:

1. Farid HA, Sayed RH, El-Shamarka ME, Abdel-Salam OME, El Sayed NS. PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson's disease in rats. Inflammopharmacology. 2023 Aug 4. doi: 10.1007/s10787-023-01305-x. Epub ahead of print. PMID: 37541971. 2. Patel P, Patel S, Chudasama P, Soni S, Raval M. Roflumilast ameliorates diabetic nephropathy in rats through down-regulation of JAK/STAT signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 15. doi: 10.1007/s00210-023-02535-0. Epub ahead of print. PMID: 37318524.

1: Oba Y, Lone NA. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ther Adv Respir Dis. 2013 Feb;7(1):13-24. doi: 10.1177/1753465812466167. Epub 2012 Nov 29. Review. PubMed PMID: 23197074. 2: Taegtmeyer AB, Leuppi JD, Kullak-Ublick GA. Roflumilast--a phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD. Swiss Med Wkly. 2012 Jul 25;142:w13628. doi: 10.4414/smw.2012.13628. Review. PubMed PMID: 22833385. 3: Reid DJ, Pham NT. Roflumilast: a novel treatment for chronic obstructive pulmonary disease. Ann Pharmacother. 2012 Apr;46(4):521-9. doi: 10.1345/aph.1Q646. Epub 2012 Mar 20. Review. PubMed PMID: 22433610. 4: Pinner NA, Hamilton LA, Hughes A. Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. Clin Ther. 2012 Jan;34(1):56-66. doi: 10.1016/j.clinthera.2011.12.008. Review. PubMed PMID: 22284994. 5: Lahu G, Nassr N, HÃ¼nnemeyer A. Pharmacokinetic evaluation of roflumilast. Expert Opin Drug Metab Toxicol. 2011 Dec;7(12):1577-91. doi: 10.1517/17425255.2011.632409. Epub 2011 Nov 8. Review. PubMed PMID: 22059647. 6: Izquierdo Alonso JL. [Phosphodiesterase-4 inhibitors: roflumilast]. Rev Clin Esp. 2011 Mar;211 Suppl 2:22-30. doi: 10.1016/S0014-2565(11)70008-X. Review. Spanish. PubMed PMID: 21596170. 7: Antoniu SA. New therapeutic options in the management of COPD - focus on roflumilast. Int J Chron Obstruct Pulmon Dis. 2011;6:147-55. doi: 10.2147/COPD.S7336. Epub 2011 Feb 17. Review. PubMed PMID: 21468165; PubMed Central PMCID: PMC3064419. 8: Roflumilast for severe COPD? Drug Ther Bull. 2011 Apr;49(4):45-8; quiz iii-iv. doi: 10.1136/dtb.2011.02.0025. Review. PubMed PMID: 21467576. 9: Izquierdo Alonso JL. [Clinical profile of roflumilast]. Arch Bronconeumol. 2010 Dec;46 Suppl 10:25-32. doi: 10.1016/S0300-2896(10)70053-3. Review. Spanish. PubMed PMID: 21316553. 10: Cortijo Gimeno J, Morcillo SÃ¡nchez E. [Pharmacological profile of roflumilast]. Arch Bronconeumol. 2010 Dec;46 Suppl 10:19-24. doi: 10.1016/S0300-2896(10)70052-1. Review. Spanish. PubMed PMID: 21316552.