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New indication for old drug
A new indication for old drug
• Ethyl-6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-[(phenylthio)methyl]-indole-3-carboxylate hydrochloride monohydrate is widely used in Russia for prevention and treatment of flu and other viral infections.
• 26,35 million of packs of Arbidol® were sold in 2008 .
A new target
MC-101 inhibits protein kinase C alpha (PKCα)
A new target
The same specificity shows major metabolite МС-109
MC-101 inhibits NFkappaB
A possible role of MC-101 in inflammation process
Pic. from «Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease» M.R. Edwards et al. / Pharmacology & Therapeutics 121 (2009) 1–13
МС-101
A possible role of MC-101 in inflammation process
Pic. from Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease M.R. Edwards et al. / Pharmacology & Therapeutics 121 (2009) 1–13
МС-101
The most promising new indication for MC-101 is asthma
• MC—101 shows anti-inflammatory activity.
• Viral infections cause more than half of allcases of asthma attacks. MC-101 has a hugeadvantage because of its antiviral activity.
MC-101 was evaluated for possible inhibition of airway hyperresponsiveness
in mice. The ovalbumin (OVA)-sensitized animals, 10 animals per group, were
challenged by nasal inhalation with aerosolized 5% OVA for 25 min on Days 21,
23, and 25. The mice received vehicle, reference standard (Dexamethasone, 3
mg/kg) or MC-101 by gavage (PO) once daily from day 21 to day 26, preceding
ovalbumin aerosol challenge by 60 min on days 21, 23 and 25 as well as
methacholine challenge on day 26. Noninvasive measurements of airway
responsiveness were performed by using whole body plethysmography, using
increases in enhanced pause (Penh) as an index of airway obstruction.
Responses to inhaled methacholine were measured and calculated as
percentage of respective baseline values.
Asthma animal model
MC-101Dexametasone
Respiratory parameters measured by whole body plethysmography
Respiratory parameters measured by whole body plethysmography
Complex index Pehnfor evaluation of respiratory parameters
МС-101 reduces bronchoconstriction
MC-101 reduces quantity of lymphocytes in BALF
Especially eosinophils
Also MC-101 reduces concentration of proinflammatory cytokines
Also MC-101 reduces concentration of proinflammatory cytokines
Anti-asthmatic potency of MC-101
• An open-label stratified randomized parallel group study conducted at the PulmonologyResearch Institute (Moscow, Russia) under the direction of Prof. Alexander Chuchalin, President of Russian Association of Pulmonologists. The purpose was to evaluate anti-asthmatic potency of MC-101.
Trial groups
• The experimental group (12 patients) –Arbidol® 100 mg twice a day plus short acting beta agonists (SABA)
• The comparator group (12 patients) -Singular® 10 mg once a day plus short acting beta agonists (SABA)
• The control group (12 patients) – short acting beta agonists (SABA)
Trial targets
• Reduction of asthma attack quantity
• Improvement of spirography parameters
• Reduction of medium SABA dose.
Groups description
Experimental group
Control group Comparator group
Age 49,1±6,2 years 41,4±9,5 years 48,8±8,9 years
Sex(number/portion)
M 3/0,25 M 1/0,08 M 2/0,17
F 9/0,75 F 11/0,92 F 10/0,83
Asthma duration 8,3±4,2 years 8,6±4,2 years 8,1±2,8 years
Measurement of peak flow and spirographyin experimental group
(Wilkinson criteria)
Visits 0-14/14-28 days
14-28/28-42 days
0-14/28-42 days
W p< W p< W p<
Medium peak flow
Morning 20
un
relia
ble 75 0,02 72 0,02
Evening -5 58 0,052 52 0,02
FVC 55 0,052FEV1 56 0,052
FEV1%л 58 0,02
Measurement of peak flow and spirographyin control group
(Wilkinson criteria)
Visits 0-14/14-28 days
14-28/28-42 days
0-14/28-42 days
W p< W p< W p<
Medium peak flow
Morning -43
no
d
iffe
ren
ce -44
no
d
iffe
ren
ce -46
Evening -48 -20 -72
FVC -11
no
d
iffe
ren
ce
FEV1 -60
FEV1%л -51
Measurement of peak flow and spirographyin comparator group
(Wilkinson criteria)
Visits 0-14/14-28 days
14-28/28-42 days
0-14/28-42 days
W p< W p< W p<
Medium peak flow Morning 70 0,02 26 70 78 0,02
Evening 65 0,02 38 65 78 0,02
FVC 52 0,02FEV1 72 0,02
FEV1%л 54 0,052
Dynamics of frequency of asthma attacks
0
2
4
6
8
10
decreased increased remain the same
experimental group
control group
comparator group
Nu
mb
er
of
pat
ien
ts
Administration of Arbidol and Syngular reduce frequency of asthma attacks
Dynamics of frequency of SABA inhalations
0
2
4
6
8
10
12
decreased increased remain the same
Nu
mb
er o
f p
atie
nts
experimental group
control group
comparator group
Administration of Arbidol and Syngular reduce frequency of SABA inhalations
Results
• Oral administration of MC-101 in the dose of100 mg twice a day within 28 days improvesclinical course of bronchial asthma of light andaverage severity, reducing the frequency ofasthma attacks and requirement of using ofshort acting beta agonists. Effectiveness of thedrug was shown by the measurement of peakflow and spirography (FVC, FEV1, FEV1%).
• No negative side effects have been revealed.
