InterPAD - DETAILS

Erlotinib, 183321-74-6, N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine, Tarceva, Erlotinib free base, 4-Quinazolinamine, N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-, OSI-774, 4-[(3-Ethynylphenyl)amino]-6,7-bis(2-methoxyethoxy)quinazoline, erlotinibum, N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, UNII-J4T82NDH7E, J4T82NDH7E, DTXSID8046454, Erlotinib, Free Base, HSDB 8082, OSI 744, CHEBI:114785, CP-358,774, 183321-74-6 (free base), CHEMBL553, RG-1415, [6,7-BIS(2-METHOXY-ETHOXY)QUINAZOLINE-4-YL]-(3-ETHYNYLPHENYL)AMINE, CP-358774, DTXCID6026454, CP-35877401, NSC 718781, R 1415, R-1415, MFCD02089651, NCGC00164574-01, [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine, Erlotinib(Tarceva), 1429636-49-6, CAS-183321-74-6, Erlotinib [INN:BAN], SR-05000001460, CP358774, Erotinib, (6,7-bis(2-methoxy-ethoxy)quinazoline-4-yl)-(3-ethynylphenyl)amine, (6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl)-(3-ethynyl-phenyl)-amine, nchembio866-comp3, Erlotinib free base?, Kinome_3317, n-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine monohydrochloride, ERLOTINIB [MI], ERLOTINIB [VANDF], ERLOTINIB [WHO-DD], SCHEMBL8413, ERLOTINIB [EMA EPAR], BDBM5446, cid_176870, GTPL4920, L01XE03, AAKJLRGGTJKAMG-UHFFFAOYSA-N, HMS2089F05, HMS3244M19, HMS3244M20, HMS3244N19, HMS3295A19, HMS3713C22, HMS3745M05, Tox21_112202, AC-399, NSC800097, s7786, STK623143, AKOS000282911, Tox21_112202_1, CCG-220420, CS-0620, DB00530, NSC-800097, Ro-508231, SB16916, NCGC00164574-03, NCGC00164574-05, NCGC00164574-06, NCGC00164574-14, NCGC00164574-25, AS-35132, BCB03_000783, BE164419, HY-50896, SY028059, AM20090621, FT-0651539, NS00006169, EN300-708808, K00241, AB01273955-01, AB01273955-02, AB01273955-03, Q418369, SR-05000001460-1, SR-05000001460-2, SR-05000001460-3, SR-05000001460-6, BRD-K70401845-003-04-7, Z2588038919

No.	Title	Href
1	Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer. 2015 Sep 15;137(6):1446-56. doi: 10.1002/ijc.29483.	`Click`
2	Luteolin enhances erlotinib's cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines. Front Pharmacol. 2022 Sep 19;13:952169. doi: 10.3389/fphar.2022.952169.	`Click`
3	Kaempferol potentiates the sensitivity of pancreatic cancer cells to erlotinib via inhibition of the PI3K/AKT signaling pathway and epidermal growth factor receptor. Inflammopharmacology. 2021 Oct;29(5):1587-1601. doi: 10.1007/s10787-021-00848-1.	`Click`
4	Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth. Cell Death Dis. 2018 Feb 15;9(3):262. doi: 10.1038/s41419-018-0314-6.	`Click`
5	Capsaicin enhances erlotinib-induced cytotoxicity via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells. Toxicol Res (Camb). 2019 Mar 12;8(3):459-470. doi: 10.1039/c8tx00346g.	`Click`
6	β-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer. Pharmacol Res. 2023 May;191:106739. doi: 10.1016/j.phrs.2023.106739.	`Click`
7	Antitumor effects of erlotinib in combination with berberine in A431 cells. BMC Pharmacol Toxicol. 2023 May 11;24(1):29. doi: 10.1186/s40360-023-00661-2.	`Click`
8	Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells. Cell Physiol Biochem. 2018;49(4):1615-1632. doi: 10.1159/000493497.	`Click`
9	Alantolactone sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3 signaling. Mol Carcinog. 2019 Apr;58(4):565-576. doi: 10.1002/mc.22951.	`Click`

No.

Title

Href

Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer. 2015 Sep 15;137(6):1446-56. doi: 10.1002/ijc.29483.

Click

Luteolin enhances erlotinib's cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines. Front Pharmacol. 2022 Sep 19;13:952169. doi: 10.3389/fphar.2022.952169.

Click

Kaempferol potentiates the sensitivity of pancreatic cancer cells to erlotinib via inhibition of the PI3K/AKT signaling pathway and epidermal growth factor receptor. Inflammopharmacology. 2021 Oct;29(5):1587-1601. doi: 10.1007/s10787-021-00848-1.

Click

Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth. Cell Death Dis. 2018 Feb 15;9(3):262. doi: 10.1038/s41419-018-0314-6.

Click

Capsaicin enhances erlotinib-induced cytotoxicity via AKT inactivation and excision repair cross-complementary 1 (ERCC1) down-regulation in human lung cancer cells. Toxicol Res (Camb). 2019 Mar 12;8(3):459-470. doi: 10.1039/c8tx00346g.

Click

β-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer. Pharmacol Res. 2023 May;191:106739. doi: 10.1016/j.phrs.2023.106739.

Click

Antitumor effects of erlotinib in combination with berberine in A431 cells. BMC Pharmacol Toxicol. 2023 May 11;24(1):29. doi: 10.1186/s40360-023-00661-2.

Click

Repression of PDK1- and LncRNA HOTAIR-Mediated EZH2 Gene Expression Contributes to the Enhancement of Atractylenolide 1 and Erlotinib in the Inhibition of Human Lung Cancer Cells. Cell Physiol Biochem. 2018;49(4):1615-1632. doi: 10.1159/000493497.

Click

Alantolactone sensitizes human pancreatic cancer cells to EGFR inhibitors through the inhibition of STAT3 signaling. Mol Carcinog. 2019 Apr;58(4):565-576. doi: 10.1002/mc.22951.

Click

Name	Erlotinib
PubChem CID	176870
Molecular Weight	393.4g/mol
Synonyms	Erlotinib, 183321-74-6, N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine, Tarceva, Erlotinib free base, 4-Quinazolinamine, N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-, OSI-774, 4-[(3-Ethynylphenyl)amino]-6,7-bis(2-methoxyethoxy)quinazoline, erlotinibum, N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, UNII-J4T82NDH7E, J4T82NDH7E, DTXSID8046454, Erlotinib, Free Base, HSDB 8082, OSI 744, CHEBI:114785, CP-358,774, 183321-74-6 (free base), CHEMBL553, RG-1415, [6,7-BIS(2-METHOXY-ETHOXY)QUINAZOLINE-4-YL]-(3-ETHYNYLPHENYL)AMINE, CP-358774, DTXCID6026454, CP-35877401, NSC 718781, R 1415, R-1415, MFCD02089651, NCGC00164574-01, [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine, Erlotinib(Tarceva), 1429636-49-6, CAS-183321-74-6, Erlotinib [INN:BAN], SR-05000001460, CP358774, Erotinib, (6,7-bis(2-methoxy-ethoxy)quinazoline-4-yl)-(3-ethynylphenyl)amine, (6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4-yl)-(3-ethynyl-phenyl)-amine, nchembio866-comp3, Erlotinib free base?, Kinome_3317, n-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine monohydrochloride, ERLOTINIB [MI], ERLOTINIB [VANDF], ERLOTINIB [WHO-DD], SCHEMBL8413, ERLOTINIB [EMA EPAR], BDBM5446, cid_176870, GTPL4920, L01XE03, AAKJLRGGTJKAMG-UHFFFAOYSA-N, HMS2089F05, HMS3244M19, HMS3244M20, HMS3244N19, HMS3295A19, HMS3713C22, HMS3745M05, Tox21_112202, AC-399, NSC800097, s7786, STK623143, AKOS000282911, Tox21_112202_1, CCG-220420, CS-0620, DB00530, NSC-800097, Ro-508231, SB16916, NCGC00164574-03, NCGC00164574-05, NCGC00164574-06, NCGC00164574-14, NCGC00164574-25, AS-35132, BCB03_000783, BE164419, HY-50896, SY028059, AM20090621, FT-0651539, NS00006169, EN300-708808, K00241, AB01273955-01, AB01273955-02, AB01273955-03, Q418369, SR-05000001460-1, SR-05000001460-2, SR-05000001460-3, SR-05000001460-6, BRD-K70401845-003-04-7, Z2588038919
Drug Type	Small molecule
Formula	C₂₂H₂₃N₃O₄
SMILES	COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC
InChI	1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
InChIKey	AAKJLRGGTJKAMG-UHFFFAOYSA-N
CAS Number	183321-74-6
ChEMBL ID	CHEMBL553
ChEBI ID	CHEBI:114785
TTD ID	D07POC
Drug Bank ID	DB00530
Toxicity	Organism	Test Type	Route(Dose)
	rat	LD50	intraperitoneal(165 mg/kg)
	mouse	LD50	intraperitoneal(254 mg/kg)
	rat	LD50	oral(322 mg/kg)
Structure			Download 2D MOL 3D MOL

Pair Name	Shikonin, Erlotinib
Partner Name	Shikonin
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	PLCG1	hsa5335
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
	DK-MG	Glioblastoma	Homo sapiens (Human)	CVCL_1173
	SNB-19	Astrocytoma	Homo sapiens (Human)	CVCL_0535
	BS153	Glioblastoma	Homo sapiens (Human)	CVCL_S444
	A-172	Glioblastoma	Homo sapiens (Human)	CVCL_0131
	T98G	Glioblastoma	Homo sapiens (Human)	CVCL_0556
	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
Result	These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib.

Pair Name	Luteolin, Erlotinib
Partner Name	Luteolin
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAD	hsa572
	Down-regulation	Expression	BCL-xL	hsa598
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Down-regulation	Phosphorylation	NFKB1	hsa4790
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	U-251MG	Astrocytoma	Homo sapiens (Human)	CVCL_0021
In Vitro Model	U-87MG ATCC	Glioblastoma	Homo sapiens (Human)	CVCL_0022
Result	These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV.

Pair Name	Kaempferol, Erlotinib
Partner Name	Kaempferol
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP9	hsa842
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Up-regulation	Cleavage	PARP1	hsa142
	Down-regulation	Expression	PIK3CA	hsa5290
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
In Vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0186
In Vivo Model	The in vivo results revealed that treatment combination of KAE and ERL further reduced the volume and weight of subcutaneous grafted tumors.
Result	These data imply that KAE may be a valid therapeutic candidate to potentiate PC cell sensitivity to ERL via inhibiting PI3K/AKT and EGFR signaling.

Pair Name	Gambogenic acid, Erlotinib
Partner Name	Gambogenic acid
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	FGFR3	hsa2261
	Down-regulation	Phosphorylation	FRS2	hsa10818
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	RPS6	hsa6194
In Vitro Model	HCC827	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_2063
	HCC827 ER1	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_EJ07
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1483
In Vivo Model	The human cell-derived tumor xenografts (CDX) were established by s.c. injecting 0.2 ml of the tumor cell suspension (1×10⁷ cells) mixed 1:1 with Matrigel (Becton Dickinson).
Result	Our findings provide preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy when used as a combined administration.

Pair Name	Capsaicin, Erlotinib
Partner Name	Capsaicin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
Gene Regulation	Down-regulation	Expression	ERCC1	hsa2067
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
Result	These results may provide a rationale to combine capsaicin with erlotinib for lung cancer treatment.

Pair Name	Beta-Elemene, Erlotinib
Partner Name	Beta-Elemene
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Up-regulation	Expression	H19	KEGG ID N.A.
In Vitro Model	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
	NCI-H1650	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1483
	NCI-H1819	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1497
In Vivo Model	5×10⁶ H1975 shRNA-NC cells or H1975 H19-shRNA cells were injected subcutaneously into 6-week-old female nude mice in the right flanks.
Result	Our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Pair Name	Berberine, Erlotinib
Partner Name	Berberine
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Phosphorylation	EGFR	hsa1956
	Down-regulation	Phosphorylation	MAPK1	hsa5594
In Vitro Model	A-431	Skin squamous cell carcinoma	Homo sapiens (Human)	CVCL_0037
	NCI-H1666	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1485
	NCI-H441	Lung papillary adenocarcinoma	Homo sapiens (Human)	CVCL_1561
	NCI-H1781	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1494
In Vivo Model	A431 cells (5×10⁶) were suspended in 200 µL of normal saline and subcutaneously implanted into 6-7-week-old male athymic nude mice.
Result	Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors.

Pair Name	Atractylenolide I, Erlotinib
Partner Name	Atractylenolide I
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Gene Regulation	Down-regulation	Expression	CYB5R2	hsa51700
Gene Regulation	Down-regulation	Expression	EZH2	hsa2146
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vitro Model	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
In Vivo Model	A549 cells, carrying the luciferase reporter gene (1×10⁷ cells), were subcutaneously injectinto the mice.
Result	Targeting the PDK1- and HOTAIR-mediated downstream molecule EZH2 by the combination of ATL-1 and erlotinib potentially facilitates the development of an additional novel strategy to combat lung cancer

Pair Name	Alantolactone, Erlotinib
Partner Name	Alantolactone
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Gene Regulation	Down-regulation	Expression	STAT3	hsa6774
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0186
	AsPC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0152
In Vivo Model	BxPC-3 cells (1×10⁶) in 0.1 mLPBS were injected subcutaneously into the right flank of eachmouse.
Result	Our results suggested that Alantolactone could sensitize human pancreatic cancer cells to EGFR inhibitors possibly through down-regulating the STAT3 signaling. Alantolactone, when combined with other EGFR targeted agents, could be further developed as a potential therapy for pancreatic cancer.