WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H201190
CAS#: 143851-98-3 (HCl)
Description: Elacridar, also known as GF120918A, is a P-glycoprotein (P-gp) inhibitor, and has been used both in vitro and in vivo as a tool inhibitor of P-glycoprotein (Pgp) to investigate the role of transporters in the disposition of various test molecules. In vitro, GF120918A demonstrated high plasma protein binding across species, although a definitive protein binding evaluation was precluded by poor recovery, particularly in buffer and in mouse, rat, and dog plasma. GF120918A did not demonstrate potent inhibition of several human cytochrome P450 enzymes evaluated in vitro, with IC(50) values well above concentrations anticipated to be achieved in vivo. Together, these data confirm the utility of GF120918A as a tool P-glycoprotein inhibitor in preclinical species and offer additional guidance on preclinical dose regimens likely to produce P-glycoprotein-mediated effects.
Hodoodo Cat#: H201190
Name: Elacridar HCl
CAS#: 143851-98-3 (HCl)
Chemical Formula: C34H34ClN3O5
Exact Mass: 0.00
Molecular Weight: 600.110
Elemental Analysis: C, 68.05; H, 5.71; Cl, 5.91; N, 7.00; O, 13.33
Related CAS #: 143851-98-3 (Elacridar HCl) 143664-11-3 (Elacridar)
Synonym: GF120918; GF-120918; GF 120918; GF-120918A; GF120918A; GF 120918A; GG 918; D03968. Elacridar hydrochloride.
IUPAC/Chemical Name: N-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxamide hydrochloride.
InChi Key: IQOJZZHRYSSFJM-UHFFFAOYSA-N
InChi Code: InChI=1S/C34H33N3O5.ClH/c1-40-28-9-5-7-26-32(28)36-31-25(33(26)38)6-4-8-27(31)34(39)35-24-12-10-21(11-13-24)14-16-37-17-15-22-18-29(41-2)30(42-3)19-23(22)20-37;/h4-13,18-19H,14-17,20H2,1-3H3,(H,35,39)(H,36,38);1H
SMILES Code: O=C(C(C=CC=C1C2=O)=C1NC3=C2C=CC=C3OC)NC4=CC=C(CCN5CC6=C(C=C(OC)C(OC)=C6)CC5)C=C4.[H]Cl
Appearance: Yellow 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, not in water
Shelf Life: >5 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: Related CAS# 143851-98-3 (Elacridar HCl); 143664-11-3 (Elacridar)
| Biological target: | Elacridar (GF120918, GW120918, GG918, GW0918) is a potent P-gp (MDR-1) and BCRP inhibitor. |
| In vitro activity: | Elacridar, a P-gp inhibitor, suppressed metabolite formation in enterocytes for loperamide, a substrate of CYP3A4 and P-gp, suggesting that enterocytes in suspension do not have active P-gp efflux functions, and the suppression of metabolism in enterocytes is probably caused by inhibition of CYP3A4/5 by elacridar. Reference: Drug Metab Lett. 2018;12(1):3-13. http://www.eurekaselect.com/158255/article |
| In vivo activity: | Friend leukemia virus strain B mice were administered 100 mg/kg elacridar either orally or intraperitoneally. The absolute bioavailability of elacridar after oral or intraperitoneal dosing was determined with respect to an intravenous dose of 2.5 mg/kg. At these doses, the absolute bioavailability was 0.22 for oral administration and 0.01 for intraperitoneal administration. The terminal half-life of elacridar was approximately 4 h after intraperitoneal and intravenous administration and nearly 20 h after oral dosing. The brain-to-plasma partition coefficient (Kp,brain) of elacridar increased as plasma exposure increased, suggesting saturation of the efflux transporters at the blood-brain barrier. The Kp,brain after intravenous, intraperitoneal, and oral dosing was 0.82, 0.43, and 4.31, respectively. The low aqueous solubility and high lipophilicity of elacridar result in poor oral absorption, most likely dissolution-rate-limited. These results illustrate the importance of the route of administration and the resultant plasma exposure in achieving effective plasma and brain concentrations of elacridar and can be used as a guide for future studies involving elacridar administration and in developing formulation strategies to overcome the poor absorption. Reference: Drug Metab Dispos. 2012 Aug;40(8):1612-9. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22611067/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.0 | 8.33 |
The following data is based on the product molecular weight 600.11 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: | |
| In vitro protocol: | 1. Wong S, Doshi U, Vuong P, Liu N, Tay S, Le H, Kosaka M, Kenny JR, Li AP, Yan Z. Utility of Pooled Cryopreserved Human Enterocytes as an In vitro Model for Assessing Intestinal Clearance and Drug-Drug Interactions. Drug Metab Lett. 2018;12(1):3-13. doi: 10.2174/1872312812666171213114422. PMID: 29237391. 2. Hyafil F, Vergely C, Du Vignaud P, Grand-Perret T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 1993 Oct 1;53(19):4595-602. PMID: 8402633. |
| In vivo protocol: | 1. Sane R, Agarwal S, Elmquist WF. Brain distribution and bioavailability of elacridar after different routes of administration in the mouse. Drug Metab Dispos. 2012 Aug;40(8):1612-9. doi: 10.1124/dmd.112.045930. Epub 2012 May 18. PMID: 22611067; PMCID: PMC3400790. |
1: Sato H, Siddig S, Uzu M, Suzuki S, Nomura Y, Kashiba T, Gushimiyagi K, Sekine Y, Uehara T, Arano Y, Yamaura K, Ueno K. Elacridar enhances the cytotoxic effects of sunitinib and prevents multidrug resistance in renal carcinoma cells. Eur J Pharmacol. 2015 Jan 5;746:258-66. doi: 10.1016/j.ejphar.2014.11.021. Epub 2014 Nov 29. PubMed PMID: 25455500.
2: Hendrikx JJ, Lagas JS, Wagenaar E, Rosing H, Schellens JH, Beijnen JH, Schinkel AH. Oral co-administration of elacridar and ritonavir enhances plasma levels of oral paclitaxel and docetaxel without affecting relative brain accumulation. Br J Cancer. 2014 May 27;110(11):2669-76. doi: 10.1038/bjc.2014.222. Epub 2014 Apr 29. PubMed PMID: 24781280; PubMed Central PMCID: PMC4037831.
3: Chuan Tang S, Nguyen LN, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH. Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar. Int J Cancer. 2014 Mar 15;134(6):1484-94. doi: 10.1002/ijc.28475. Epub 2013 Oct 3. PubMed PMID: 24037730.
4: Pajeva IK, Sterz K, Christlieb M, Steggemann K, Marighetti F, Wiese M. Interactions of the multidrug resistance modulators tariquidar and elacridar and their analogues with P-glycoprotein. ChemMedChem. 2013 Oct;8(10):1701-13. doi: 10.1002/cmdc.201300233. Epub 2013 Aug 13. PubMed PMID: 23943604.
5: Bauer M, Karch R, Zeitlinger M, Stanek J, Philippe C, Wadsak W, Mitterhauser M, Jäger W, Haslacher H, Müller M, Langer O. Interaction of 11C-tariquidar and 11C-elacridar with P-glycoprotein and breast cancer resistance protein at the human blood-brain barrier. J Nucl Med. 2013 Aug;54(8):1181-7. doi: 10.2967/jnumed.112.118232. Epub 2013 Jul 5. PubMed PMID: 23833270; PubMed Central PMCID: PMC3882137.
6: Sane R, Agarwal S, Mittapalli RK, Elmquist WF. Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system. J Pharmacol Exp Ther. 2013 Apr;345(1):111-24. doi: 10.1124/jpet.112.199786. Epub 2013 Feb 8. PubMed PMID: 23397054; PubMed Central PMCID: PMC3608446.
7: Sane R, Mittapalli RK, Elmquist WF. Development and evaluation of a novel microemulsion formulation of elacridar to improve its bioavailability. J Pharm Sci. 2013 Apr;102(4):1343-54. doi: 10.1002/jps.23450. Epub 2013 Jan 18. PubMed PMID: 23334925; PubMed Central PMCID: PMC3967790.
8: Bankstahl JP, Bankstahl M, Römermann K, Wanek T, Stanek J, Windhorst AD, Fedrowitz M, Erker T, Müller M, Löscher W, Langer O, Kuntner C. Tariquidar and elacridar are dose-dependently transported by P-glycoprotein and Bcrp at the blood-brain barrier: a small-animal positron emission tomography and in vitro study. Drug Metab Dispos. 2013 Apr;41(4):754-62. doi: 10.1124/dmd.112.049148. Epub 2013 Jan 10. PubMed PMID: 23305710.
9: Kallem R, Kulkarni CP, Patel D, Thakur M, Sinz M, Singh SP, Mahammad SS, Mandlekar S. A simplified protocol employing elacridar in rodents: a screening model in drug discovery to assess P-gp mediated efflux at the blood brain barrier. Drug Metab Lett. 2012 Jun 1;6(2):134-44. PubMed PMID: 23061481.
10: Sarisozen C, Vural I, Levchenko T, Hincal AA, Torchilin VP. Long-circulating PEG-PE micelles co-loaded with paclitaxel and elacridar (GG918) overcome multidrug resistance. Drug Deliv. 2012 Nov;19(8):363-70. doi: 10.3109/10717544.2012.724473. Epub 2012 Oct 3. PubMed PMID: 23030458.
1. Zaccara G, Schmidt D. Do traditional anti-seizure drugs have a future? A review of potential anti-seizure drugs in clinical development. Pharmacol Res. 2016 Feb;104:38-48. doi: 10.1016/j.phrs.2015.12.011. Epub 2015 Dec 12. PMID: 26689774.
