Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :28899692
Publication Date : //

In vitro efficacy of bumped kinase inhibitors against Besnoitia besnoiti tachyzoites.


Besnoitia besnoiti is an apicomplexan parasite responsible for bovine besnoitiosis, a chronic and debilitating disease that causes systemic and skin manifestations and sterility in bulls. Neither treatments nor vaccines are currently available. In the search for therapeutic candidates, calcium-dependent protein kinases have arisen as promising drug targets in other apicomplexans (e.g. Neospora caninum, Toxoplasma gondii, Plasmodium spp. and Eimeria spp.) and are effectively targeted by bumped kinase inhibitors. In this study, we identified and cloned the gene coding for BbCDPK1. The impact of a library of nine bumped kinase inhibitor analogues on the activity of recombinant BbCDPK1 was assessed by luciferase assay. Afterwards, those were further screened for efficacy against Besnoitiabesnoiti tachyzoites grown in Marc-145 cells. Primary tests at 5µM revealed that eight compounds exhibited more than 90% inhibition of invasion and proliferation. The compounds BKI 1294, 1517, 1553 and 1571 were further characterised, and EC (1294: 2.38µM; 1517: 2.20µM; 1553: 3.34µM; 1571: 2.78µM) were determined by quantitative real-time polymerase chain reaction in 3-day proliferation assays. Exposure of infected cultures with EC concentrations of these drugs for up to 48h was not parasiticidal. The lack of parasiticidal action was confirmed by transmission electron microscopy, which showed that bumped kinase inhibitor treatment interfered with cell cycle regulation and non-disjunction of tachyzoites, resulting in the formation of large multi-nucleated complexes which co-existed with viable parasites within the parasitophorous vacuole. However, it is possible that, in the face of an active immune response, parasite clearance may occur. In summary, bumped kinase inhibitors may be effective drug candidates to control Besnoitiabesnoiti infection. Further in vivo experiments should be planned, as attainment and maintenance of therapeutic blood plasma levels in calves, without toxicity, has been demonstrated for BKIs 1294, 1517 and 1553.

Authors : Jiménez-Meléndez Alejandro , Ojo Kayode K , Wallace Alexandra M , Smith Tess R , Hemphill Andrew , Balmer Vreni , Regidor-Cerrillo Javier , Ortega-Mora Luis M , Hehl Adrian B , Fan Erkang , Maly Dustin J , Van Voorhis Wesley C , Álvarez-García Gema ,

Related products :

Catalog number Product name Quantity
VET-B021-96D Besnoitia spp. PCR detection kit, Bovine, DNA 48rxs
VET-B021-96D Besnoitia spp. PCR detection kit, Bovine, DNA 96rxs
EKIN-400 EnzyChrom™ Kinase Assay Kit, Rapid mix-and-measure procedure for determination of kinase activity and high-throµghput screening for kinase inhibitors by fluorimetric (530nm_590nm) method 400Tests
OBT0969 GOAT ANTI TOXOPLASMA GONDII TACHYZOITES, Product Type Polyclonal Antibody, Specificity TOXOPLASMA GONDII TACHYZOITES, Target Species Protozoan, Host Goat, Format Purified, Isotypes Polyclonal Ig 1 ml
SCH-OBT0969 GOAT ANTI TOXOPLASMA GONDII TACHYZOITES, Product Type Polyclonal Antibody, Specificity TOXOPLASMA GONDII TACHYZOITES, Target Species Protozoan, Host Goat, Format Purified, Isotypes Polyclonal Ig 1 ml
EKIN-400 EnzyChrom™ Kinase Assay Kit, Rapid mix-and-measure procedure for determination of kinase activity and high-throµghput screening for kinase inhibitors by fluorimetric (530nm_590nm) method. Procedure 1 400tests
orb61342 GW2580, Free Base GW2580 is a small-molecule inhibitor of cFMS kinase; at 60 nM it inhibited human cFMS kinase completely in vitro and was inactive against 26 other kinases. For research use only. 300 mg
PKA-PKI-500 Kinase inhibitors PKI, heat-stable protein kinase inhibitor of PKA (rabbit) 500
PKA-PKI-100 Kinase inhibitors PKI, heat-stable protein kinase inhibitor of PKA (rabbit) 100
orb60838 AZ 960 AZ 960 is a novel small molecule JAK2 kinase inhibitor with an IC50 and Ki of 3 mM and 0.45 nM in vitro, respectively. For research use only. 10 mg
orb80800 Human MAPK1 protein MAPK1 Recombinant (extracellular signal-regulated kinase) Mitogen-Activated Protein Kinase, is highly active form produced by phosphorylation of the purified ERK2_MAPK1 in vitro wi 3
RG-1001 CyAL-5 cRGD, fluorescence imaging agent for target of avЯ3 expression in the neovasculature, tumor cells, angiogenesis growth and treatment efficacy
PKA-PKI-100 Kinase inhibitors: PKI, heat-stable protein kinase inhibitor of PKA (rabbit), protein, CAS number: UniProtKB: P61926, Chemical name: recombinantly expressed in E.coli 100
PKA-PKI-500 Kinase inhibitors: PKI, heat-stable protein kinase inhibitor of PKA (rabbit), protein, CAS number: UniProtKB: P61926, Chemical name: recombinantly expressed in E.coli 500
PKI-PP2-001 Kinase inhibitors PP2 1 mg
PKI-ML9-010 Kinase inhibitors ML-9 10 mg
PKI-ML9-005 Kinase inhibitors ML-9 5 mg
PKI-W7-025 Kinase inhibitors W-7 25 mg
PKI-TBB-010 Kinase inhibitors TBB 10 mg
PKI-DRB-100 Kinase inhibitors DRB 100
PKI-PP1-001 Kinase inhibitors PP1 1 mg
PKI-W7-050 Kinase inhibitors W-7 50 mg
PKI-LUT-100 Kinase inhibitors Luteolin 100 mg
PKI-ERK-005 Kinase inhibitors Erk Inhibitor 5 mg
PKI-TCN-005 Kinase inhibitors Triciribine 5 mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur