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MedKoo Cat#: 201190 | Name: Elacridar HCl
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Description:

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

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.

Chemical Structure

Elacridar HCl
Elacridar HCl
CAS#143851-98-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 201190

Name: Elacridar HCl

CAS#: 143851-98-3 (HCl)

Chemical Formula: C34H34ClN3O5

Exact Mass: 0.0000

Molecular Weight: 600.11

Elemental Analysis: C, 68.05; H, 5.71; Cl, 5.91; N, 7.00; O, 13.33

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to Ship
200mg USD 1,250.00 Ready to Ship
500mg USD 2,650.00 Ready to Ship
1g USD 4,250.00 Ready to Ship
2g USD 6,450.00 Ready to ship
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Related CAS #
143851-98-3 (HCl) 143664-11-3 (free base)
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 mg/mL mM
Solubility
DMSO 5.0 8.33
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 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.

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. 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: Mollazadeh S, Sahebkar A, Hadizadeh F, Behravan J, Arabzadeh S. Structural and functional aspects of P-glycoprotein and its inhibitors. Life Sci. 2018 Dec 1;214:118-123. doi: 10.1016/j.lfs.2018.10.048. Epub 2018 Oct 27. PMID: 30449449. 2: Dash RP, Jayachandra Babu R, Srinivas NR. Therapeutic Potential and Utility of Elacridar with Respect to P-glycoprotein Inhibition: An Insight from the Published In Vitro, Preclinical and Clinical Studies. Eur J Drug Metab Pharmacokinet. 2017 Dec;42(6):915-933. doi: 10.1007/s13318-017-0411-4. PMID: 28374336. 3: Alves R, Gonçalves AC, Jorge J, Almeida AM, Sarmento-Ribeiro AB. Combination of Elacridar with Imatinib Modulates Resistance Associated with Drug Efflux Transporters in Chronic Myeloid Leukemia. Biomedicines. 2022 May 17;10(5):1158. doi: 10.3390/biomedicines10051158. PMID: 35625893; PMCID: PMC9138473. 4: Nieto Montesinos R, Béduneau A, Lamprecht A, Pellequer Y. Liposomes Coloaded with Elacridar and Tariquidar To Modulate the P-Glycoprotein at the Blood-Brain Barrier. Mol Pharm. 2015 Nov 2;12(11):3829-38. doi: 10.1021/acs.molpharmaceut.5b00002. Epub 2015 Sep 29. PMID: 26390138. 5: 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. PMID: 25455500. 6: 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. 7: Wen LJ, Wang YS, Zhang J. Nano-gold micelles loaded Dox and Elacridar for reversing drug resistance of breast cancer. IET Nanobiotechnol. 2023 Apr;17(2):49-60. doi: 10.1049/nbt2.12102. Epub 2022 Nov 7. PMID: 36341719; PMCID: PMC10116014. 8: 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. PMID: 23334925; PMCID: PMC3967790. 9: Karbownik A, Sobańska K, Płotek W, Grabowski T, Klupczynska A, Plewa S, Grześkowiak E, Szałek E. The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid. Invest New Drugs. 2020 Jun;38(3):574-583. doi: 10.1007/s10637-019-00806-3. Epub 2019 Jun 8. PMID: 31177402; PMCID: PMC7211195. 10: Chen H, Shien K, Suzawa K, Tsukuda K, Tomida S, Sato H, Torigoe H, Watanabe M, Namba K, Yamamoto H, Soh J, Asano H, Miyoshi S, Toyooka S. Elacridar, a third-generation ABCB1 inhibitor, overcomes resistance to docetaxel in non-small cell lung cancer. Oncol Lett. 2017 Oct;14(4):4349-4354. doi: 10.3892/ol.2017.6678. Epub 2017 Jul 26. PMID: 28959367; PMCID: PMC5607652. 11: Suzuki K, Taniyama K, Aoyama T, Watanabe Y. Evaluation of the Role of P-glycoprotein (P-gp)-Mediated Efflux in the Intestinal Absorption of Common Substrates with Elacridar, a P-gp Inhibitor, in Rats. Eur J Drug Metab Pharmacokinet. 2020 Jun;45(3):385-392. doi: 10.1007/s13318-019-00602-7. PMID: 32078103. 12: Sawicki E, Schellens JH, Beijnen JH, Nuijen B. Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof- of-concept clinical studies. Drug Dev Ind Pharm. 2017 Apr;43(4):584-594. doi: 10.1080/03639045.2016.1274901. Epub 2017 Jan 8. PMID: 28010129. 13: 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. PMID: 23833270; PMCID: PMC3882137. 14: Giacone DV, Carvalho VFM, Costa SKP, Lopes LB. Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition. J Pharm Sci. 2018 Feb;107(2):698-705. doi: 10.1016/j.xphs.2017.09.007. Epub 2017 Sep 19. PMID: 28935591. 15: Sawicki E, Verheijen RB, Huitema AD, van Tellingen O, Schellens JH, Nuijen B, Beijnen JH, Steeghs N. Clinical pharmacokinetics of an amorphous solid dispersion tablet of elacridar. Drug Deliv Transl Res. 2017 Feb;7(1):125-131. doi: 10.1007/s13346-016-0346-3. PMID: 27864786. 16: Bauer M, Blaickner M, Philippe C, Wadsak W, Hacker M, Zeitlinger M, Langer O. Whole-Body Distribution and Radiation Dosimetry of 11C-Elacridar and 11C-Tariquidar in Humans. J Nucl Med. 2016 Aug;57(8):1265-8. doi: 10.2967/jnumed.116.175182. Epub 2016 Apr 14. PMID: 27081167. 17: Verheijen RB, Yaqub M, Sawicki E, van Tellingen O, Lammertsma AA, Nuijen B, Schellens JHM, Beijnen JH, Huitema ADR, Hendrikse NH, Steeghs N. Molecular Imaging of ABCB1 and ABCG2 Inhibition at the Human Blood-Brain Barrier Using Elacridar and 11C-Erlotinib PET. J Nucl Med. 2018 Jun;59(6):973-979. doi: 10.2967/jnumed.117.195800. Epub 2017 Nov 24. PMID: 29175983. 18: Wang Y, Sparidans RW, Wang J, Li W, Lebre MC, Beijnen JH, Schinkel AH. Rifampin and ritonavir increase oral availability and elacridar enhances overall exposure and brain accumulation of the NTRK inhibitor larotrectinib. Eur J Pharm Biopharm. 2022 Jan;170:197-207. doi: 10.1016/j.ejpb.2021.12.007. Epub 2021 Dec 21. PMID: 34952136. 19: Goutal S, Langer O, Auvity S, Andrieux K, Coulon C, Caillé F, Gervais P, Cisternino S, Declèves X, Tournier N. Intravenous infusion for the controlled exposure to the dual ABCB1 and ABCG2 inhibitor elacridar in nonhuman primates. Drug Deliv Transl Res. 2018 Jun;8(3):536-542. doi: 10.1007/s13346-017-0472-6. PMID: 29294257. 20: Vicente B, López-Abán J, Chaccour J, Hernández-Goenaga J, Nicolas P, Fernández-Soto P, Muro A, Chaccour C. The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice. Sci Rep. 2021 Feb 24;11(1):4476. doi: 10.1038/s41598-021-84009-y. PMID: 33627744; PMCID: PMC7904857.
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.