Lapatinib (free base)
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MedKoo CAT#: 100490A

CAS#: 231277-92-2 (free base)

Description: Lapatinib is a synthetic, orally-active quinazoline with potential antineoplastic activity. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types. Check for active clinical trials or closed clinical trials using this agent.


Chemical Structure

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Lapatinib (free base)
CAS# 231277-92-2 (free base)

Theoretical Analysis

MedKoo Cat#: 100490A
Name: Lapatinib (free base)
CAS#: 231277-92-2 (free base)
Chemical Formula: C29H26ClFN4O4S
Exact Mass: 580.13473
Molecular Weight: 581.06
Elemental Analysis: C, 59.94; H, 4.51; Cl, 6.10; F, 3.27; N, 9.64; O, 11.01; S, 5.52

Price and Availability

Size Price Availability Quantity
25.0mg USD 55.0 Ready to ship
100.0mg USD 105.0 Ready to ship
500.0mg USD 150.0 Ready to ship
1.0g USD 250.0 Ready to ship
2.0g USD 450.0 Ready to ship
5.0g USD 850.0 Ready to ship
10.0g USD 1450.0 Ready to ship
20.0g USD 2250.0 Ready to ship
50.0g USD 4250.0 Ready to ship
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Related CAS #: 388082-77-7 (ditosylate)   231277-92-2 (free base)    

Synonym: GSK572016; GSK-572016; GSK 572016; GW2016; GW-2016; GW 2016; Lapatinib. US brand name: Tykerb.

IUPAC/Chemical Name: N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)furan-2-yl)quinazolin-4-amine

InChi Key: BCFGMOOMADDAQU-UHFFFAOYSA-N

InChi Code: InChI=1S/C29H26ClFN4O4S/c1-40(36,37)12-11-32-16-23-7-10-27(39-23)20-5-8-26-24(14-20)29(34-18-33-26)35-22-6-9-28(25(30)15-22)38-17-19-3-2-4-21(31)13-19/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35)

SMILES Code: O=S(CCNCC1=CC=C(C2=CC3=C(NC4=CC=C(OCC5=CC=CC(F)=C5)C(Cl)=C4)N=CN=C3C=C2)O1)(C)=O

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, not in water

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

Biological target: Lapatinib (GW572016) is an inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively.
In vitro activity: Lapatinib, in combination with radiation, enhanced DNA damage in MBT-2 cells. The results of immunofluorescence staining showed the presence of γ-H2AX, which is a marker of damage to double-strand DNA (Figure 5A). The control group of cells showed the complete absence or least number of γ-H2AX foci (0±0.01/cell); the cells receiving only radiation showed signs of DNA damage with γ-H2AX foci of 14.2±0.35/cell at 30 min; treatment with lapatinib alone was ineffective in causing DNA damage and resulted in no alterations in γ-H2AX foci (0±0.25/cell). However, in MBT-2 cells pretreated with lapatinib and exposed to radiation, there was a significant increase in the number of γ-H2AX foci (22.1±0.50/cell) (P<0.001) compared with cells exposed to radiation alone (14.2±0.35/cell). The results of Western blot showed a dose-dependent change in the levels of γ-H2AX in cells pretreated with lapatinib (50 and 100 nM) followed by radiation of dose 2.5 and 10 Gy (Figure 5B). Reference: Med Sci Monit. 2018 Aug 20;24:5811-5819. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113922/
In vivo activity: The outcomes of lapatinib treatment of tumor xenografts in an animal model showed that a daily dose of lapatinib (oral, 200 mg/kg/day) for seven days, combined with radiation on the fourth day caused a significant suppression in the growth of xenografts tumors compared with irradiation alone (Figure 6A). The results suggested that an oral dose of lapatinib increased the radiation-mediated suppression of xenografts tumors by about 60%. The results of immunohistochemistry for expression of HER-2 and EGFR in tumors recovered from mice at the end of treatment protocol of seven days showed the involvement of radiation in enhancing the levels of EGFR and HER-2 (Figure 6B). However, lapatinib, in combination with radiation therapy, suppressed the radiation-mediated activation of EGFR and HER-2 in xenograft tumors. The outcomes of this in vivo experiment indicated that lapatinib induced radiosensitization by inhibiting the radiation-mediated expression of EGFR and HER-2, in addition to facilitating DNA damage. Reference: Med Sci Monit. 2018 Aug 20;24:5811-5819. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113922/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 34.42
DMSO 65.7 113.07
DMSO:PBS (pH 7.2) (1:2) 0.33 0.57

Preparing Stock Solutions

The following data is based on the product molecular weight 581.06 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: 1. Mu Y, Sun D. Lapatinib, a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and HER-2, Enhances Radiosensitivity in Mouse Bladder Tumor Line-2 (MBT-2) Cells In Vitro and In Vivo. Med Sci Monit. 2018 Aug 20;24:5811-5819. doi: 10.12659/MSM.909865. PMID: 30125265; PMCID: PMC6113922. 2. Sakai K, Maeda S, Saeki K, Nakagawa T, Murakami M, Endo Y, Yonezawa T, Kadosawa T, Mori T, Nishimura R, Matsuki N. Anti-tumour effect of lapatinib in canine transitional cell carcinoma cell lines. Vet Comp Oncol. 2018 Dec;16(4):642-649. doi: 10.1111/vco.12434. Epub 2018 Sep 23. PMID: 30246405.
In vitro protocol: 1. Mu Y, Sun D. Lapatinib, a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and HER-2, Enhances Radiosensitivity in Mouse Bladder Tumor Line-2 (MBT-2) Cells In Vitro and In Vivo. Med Sci Monit. 2018 Aug 20;24:5811-5819. doi: 10.12659/MSM.909865. PMID: 30125265; PMCID: PMC6113922. 2. Sakai K, Maeda S, Saeki K, Nakagawa T, Murakami M, Endo Y, Yonezawa T, Kadosawa T, Mori T, Nishimura R, Matsuki N. Anti-tumour effect of lapatinib in canine transitional cell carcinoma cell lines. Vet Comp Oncol. 2018 Dec;16(4):642-649. doi: 10.1111/vco.12434. Epub 2018 Sep 23. PMID: 30246405.
In vivo protocol: 1. Mu Y, Sun D. Lapatinib, a Dual Inhibitor of Epidermal Growth Factor Receptor (EGFR) and HER-2, Enhances Radiosensitivity in Mouse Bladder Tumor Line-2 (MBT-2) Cells In Vitro and In Vivo. Med Sci Monit. 2018 Aug 20;24:5811-5819. doi: 10.12659/MSM.909865. PMID: 30125265; PMCID: PMC6113922. 2. Sakai K, Maeda S, Saeki K, Nakagawa T, Murakami M, Endo Y, Yonezawa T, Kadosawa T, Mori T, Nishimura R, Matsuki N. Anti-tumour effect of lapatinib in canine transitional cell carcinoma cell lines. Vet Comp Oncol. 2018 Dec;16(4):642-649. doi: 10.1111/vco.12434. Epub 2018 Sep 23. PMID: 30246405.

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1: Bowen JM. Development of the rat model of lapatinib-induced diarrhoea. Scientifica (Cairo). 2014;2014:194185. doi: 10.1155/2014/194185. Epub 2014 Jul 7. Review. PubMed PMID: 25126444; PubMed Central PMCID: PMC4121095.

2: Wang H. Lapatinib for the treatment of breast cancer in the People's Republic of China. Onco Targets Ther. 2014 Jul 31;7:1367-73. doi: 10.2147/OTT.S60586. eCollection 2014. Review. PubMed PMID: 25114575; PubMed Central PMCID: PMC4125370.

3: Abdel-Rahman O, Fouad M. Does the use of lapatinib increase the risk of fatigue and hepatic toxicities in patients with solid tumors? A critical literature review and meta-analysis. Expert Opin Drug Saf. 2014 Aug;13(8):999-1008. doi: 10.1517/14740338.2014.921679. Epub 2014 Jun 14. Review. PubMed PMID: 24930544.

4: Nolting M, Schneider-Merck T, Trepel M. Lapatinib. Recent Results Cancer Res. 2014;201:125-43. doi: 10.1007/978-3-642-54490-3_7. Review. PubMed PMID: 24756789.

5: Gandhi MD, Agulnik M. Targeted treatment of head and neck squamous-cell carcinoma: potential of lapatinib. Onco Targets Ther. 2014 Feb 13;7:245-51. doi: 10.2147/OTT.S46933. eCollection 2014. Review. PubMed PMID: 24611017; PubMed Central PMCID: PMC3928467.

6: Bianchi GV, Duca M, Sica L, Mariani G. Metastatic breast cancer treated with lapatinib with a prolonged benefit: a case report and a review of therapeutic options available. Tumori. 2013 Nov-Dec;99(6):269e-72e. doi: 10.1700/1390.15466. Review. PubMed PMID: 24503801.

7: Botrel TE, Paladini L, Clark OA. Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis. Core Evid. 2013;8:69-78. doi: 10.2147/CE.S50474. Epub 2013 Sep 30. Review. PubMed PMID: 24115917; PubMed Central PMCID: PMC3793631.

8: Larsen PB, Kümler I, Nielsen DL. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer. Cancer Treat Rev. 2013 Nov;39(7):720-7. doi: 10.1016/j.ctrv.2013.01.006. Epub 2013 Mar 5. Review. PubMed PMID: 23481218.

9: Gross-Goupil M, Bernhard JC, Ravaud A. Lapatinib and renal cell carcinoma. Expert Opin Investig Drugs. 2012 Nov;21(11):1727-32. doi: 10.1517/13543784.2012.713935. Epub 2012 Aug 9. Review. PubMed PMID: 22876762.

10: Riemsma R, Forbes CA, Amonkar MM, Lykopoulos K, Diaz JR, Kleijnen J, Rea DW. Systematic review of lapatinib in combination with letrozole compared with other first-line treatments for hormone receptor positive(HR+) and HER2+ advanced or metastatic breast cancer(MBC). Curr Med Res Opin. 2012 Aug;28(8):1263-79. doi: 10.1185/03007995.2012.707643. Epub 2012 Jul 16. Review. PubMed PMID: 22738819.

11: Opdam FL, Guchelaar HJ, Beijnen JH, Schellens JH. Lapatinib for advanced or metastatic breast cancer. Oncologist. 2012;17(4):536-42. doi: 10.1634/theoncologist.2011-0461. Epub 2012 Apr 3. Review. PubMed PMID: 22477724; PubMed Central PMCID: PMC3336826.

12: Hurvitz SA, Kakkar R. Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer. Breast Cancer (Dove Med Press). 2012 Apr 3;4:35-51. doi: 10.2147/BCTT.S29996. Review. PubMed PMID: 24367193; PubMed Central PMCID: PMC3846547.

13: Fleeman N, Bagust A, Boland A, Dickson R, Dundar Y, Moonan M, Oyee J, Blundell M, Davis H, Armstrong A, Thorp N. Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor-positive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis. Health Technol Assess. 2011;15(42):1-93, iii-iv. doi: 10.3310/hta15420. Review. PubMed PMID: 22152751.

14: Vrdoljak E, Boban M, Ban M. Lapatinib in the treatment of HER-2 overexpressing breast cancer. J BUON. 2011 Jul-Sep;16(3):393-9. Review. PubMed PMID: 22006739.

15: Kenny LM, Lam EW. Review: lapatinib in metastatic colorectal cancer-another strategy for disease control? Clin Adv Hematol Oncol. 2011 Jun;9(6):500-1. Review. PubMed PMID: 21841752.

16: Bouchalova K, Cizkova M, Cwiertka K, Trojanec R, Friedecky D, Hajduch M. Lapatinib in breast cancer - the predictive significance of HER1 (EGFR), HER2, PTEN and PIK3CA genes and lapatinib plasma level assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Dec;154(4):281-8. Review. PubMed PMID: 21293538.

17: Merriam P, Sikov WM. Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer. Breast Cancer (Dove Med Press). 2011 Oct 26;3:139-50. doi: 10.2147/BCTT.S12150. Review. PubMed PMID: 24367183; PubMed Central PMCID: PMC3846896.

18: Giampaglia M, Chiuri VE, Tinelli A, De Laurentiis M, Silvestris N, Lorusso V. Lapatinib in breast cancer: clinical experiences and future perspectives. Cancer Treat Rev. 2010 Nov;36 Suppl 3:S72-9. doi: 10.1016/S0305-7372(10)70024-4. Review. PubMed PMID: 21129615.

19: MacFarlane RJ, Gelmon KA. Lapatinib for breast cancer: a review of the current literature. Expert Opin Drug Saf. 2011 Jan;10(1):109-21. doi: 10.1517/14740338.2011.533168. Epub 2010 Nov 20. Review. PubMed PMID: 21091041.

20: Arai H, Yamaki M, Nishimura Y. [Pharmacological profiles and clinical effects of lapatinib tosilate (Tykerb)]. Nihon Yakurigaku Zasshi. 2010 Sep;136(3):175-84. Review. Japanese. PubMed PMID: 20838021.