InterPAD - DETAILS

001, RAD, 40-O-(2-hydroxyethyl)-rapamycin, 40-O-(2-Hydroxyethyl)rapamycin, Afinitor, Certican, Everolimus, RAD, RAD 001, RAD, SDZ, RAD001, SDZ RAD, SDZ-RAD, Zortress, 159351-69-6, Votubia, 42-O-(2-Hydroxyethyl)rapamycin, RAD-001, everolimusum, CHEBI:68478, Afinitor Disperz, Rapamycin, 42-O-(2-hydroxyethyl)-, 9HW64Q8G6G, DTXSID0040599, XIENCE V, RAD 666, RAD-666, UNII-9HW64Q8G6G, DTXCID8020599, HSDB 8255, Everolimus (INN), NSC733504, NCGC00167512-01, Everolimus (RAD001), EVEROLIMUS [INN], Everolimus (~90% pure), EVEROLIMUS (MART.), EVEROLIMUS [MART.], EVEROLIMUS (USP-RS), EVEROLIMUS [USP-RS], (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.0(sup 4,9))hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.04,9)hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, EVEROLIMUS (EP MONOGRAPH), EVEROLIMUS [EP MONOGRAPH], (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-1,18-dihydroxy-12-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone, Everolimus [USAN], AfinitorDisperz, 42-O-(2-Hydroxy)ethyl rapamycin, Everolimus?, Everolimus tablets, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-1,18-dihydroxy-12-((2R)-1-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)propan-2-yl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.0(4,9))hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-((2R)-1-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)propan-2-yl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido(2,1-c)(1,4)oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, EVE - Everolimus, EVEROLIMUS [MI], EVEROLIMUS [JAN], EVEROLIMUS [VANDF], SCHEMBL4378, EVEROLIMUS [WHO-DD], EVEROLIMUS [EMA EPAR], Everolimus [USAN:INN:BAN], NVP-RAD-001, Everolimus, analytical standard, GTPL5889, RAD-001C, CHEMBL1908360, EVEROLIMUS [ORANGE BOOK], L01XE10, L04AA18, Everolimus; RAD001; SDZ-RAD, 42-O-(2-Hydroxyethyl)-rapamycin, EX-A2057, Tox21_112510, BDBM50088378, AKOS015850977, CS-0064, DB01590, AS-16971, HY-10218, CAS-159351-69-6, Q421052, Q-101413, BRD-K13514097-001-01-2, BRD-K13514097-001-05-3, dihydroxy-[(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxy-cyclohexyl]-1-methyl-ethyl]-dimethoxy-hexamethyl-[?]pentone

No.	Title	Href
1	Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells. Int J Mol Sci. 2020 Jun 4;21(11):4026. doi: 10.3390/ijms21114026.	`Click`
2	Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer. Sci China Life Sci. 2023 Feb;66(2):298-312. doi: 10.1007/s11427-022-2185-9.	`Click`
3	UCP2 inhibition induces ROS/Akt/mTOR axis: Role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism. Free Radic Biol Med. 2017 Dec;113:176-189. doi: 10.1016/j.freeradbiomed.2017.09.022.	`Click`
4	Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus. Biochem Pharmacol. 2020 May;175:113921. doi: 10.1016/j.bcp.2020.113921.	`Click`

No.

Title

Href

Chronic Sulforaphane Administration Inhibits Resistance to the mTOR-Inhibitor Everolimus in Bladder Cancer Cells. Int J Mol Sci. 2020 Jun 4;21(11):4026. doi: 10.3390/ijms21114026.

Click

Piceatannol enhances Beclin-1 activity to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer. Sci China Life Sci. 2023 Feb;66(2):298-312. doi: 10.1007/s11427-022-2185-9.

Click

UCP2 inhibition induces ROS/Akt/mTOR axis: Role of GAPDH nuclear translocation in genipin/everolimus anticancer synergism. Free Radic Biol Med. 2017 Dec;113:176-189. doi: 10.1016/j.freeradbiomed.2017.09.022.

Click

Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus. Biochem Pharmacol. 2020 May;175:113921. doi: 10.1016/j.bcp.2020.113921.

Click

Name	Everolimus
PubChem CID	6442177
Molecular Weight	958.2g/mol
Synonyms	001, RAD, 40-O-(2-hydroxyethyl)-rapamycin, 40-O-(2-Hydroxyethyl)rapamycin, Afinitor, Certican, Everolimus, RAD, RAD 001, RAD, SDZ, RAD001, SDZ RAD, SDZ-RAD, Zortress, 159351-69-6, Votubia, 42-O-(2-Hydroxyethyl)rapamycin, RAD-001, everolimusum, CHEBI:68478, Afinitor Disperz, Rapamycin, 42-O-(2-hydroxyethyl)-, 9HW64Q8G6G, DTXSID0040599, XIENCE V, RAD 666, RAD-666, UNII-9HW64Q8G6G, DTXCID8020599, HSDB 8255, Everolimus (INN), NSC733504, NCGC00167512-01, Everolimus (RAD001), EVEROLIMUS [INN], Everolimus (~90% pure), EVEROLIMUS (MART.), EVEROLIMUS [MART.], EVEROLIMUS (USP-RS), EVEROLIMUS [USP-RS], (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.0(sup 4,9))hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.04,9)hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, EVEROLIMUS (EP MONOGRAPH), EVEROLIMUS [EP MONOGRAPH], (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-1,18-dihydroxy-12-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.0(4,9)]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone, Everolimus [USAN], AfinitorDisperz, 42-O-(2-Hydroxy)ethyl rapamycin, Everolimus?, Everolimus tablets, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-1,18-dihydroxy-12-((2R)-1-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)propan-2-yl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.0(4,9))hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-((2R)-1-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)propan-2-yl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido(2,1-c)(1,4)oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone, EVE - Everolimus, EVEROLIMUS [MI], EVEROLIMUS [JAN], EVEROLIMUS [VANDF], SCHEMBL4378, EVEROLIMUS [WHO-DD], EVEROLIMUS [EMA EPAR], Everolimus [USAN:INN:BAN], NVP-RAD-001, Everolimus, analytical standard, GTPL5889, RAD-001C, CHEMBL1908360, EVEROLIMUS [ORANGE BOOK], L01XE10, L04AA18, Everolimus; RAD001; SDZ-RAD, 42-O-(2-Hydroxyethyl)-rapamycin, EX-A2057, Tox21_112510, BDBM50088378, AKOS015850977, CS-0064, DB01590, AS-16971, HY-10218, CAS-159351-69-6, Q421052, Q-101413, BRD-K13514097-001-01-2, BRD-K13514097-001-05-3, dihydroxy-[(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxy-cyclohexyl]-1-methyl-ethyl]-dimethoxy-hexamethyl-[?]pentone
Drug Type	Small molecule
Formula	C₅₃H₈₃NO₁₄
SMILES	CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OCCO)C)C)O)OC)C)C)C)OC
InChI	1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1
InChIKey	HKVAMNSJSFKALM-GKUWKFKPSA-N
CAS Number	159351-69-6
ChEMBL ID	CHEMBL1908360
ChEBI ID	CHEBI:68478
TTD ID	D0K3QS
Drug Bank ID	DB01590
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	Sulforaphane, Everolimus
Partner Name	Sulforaphane
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	CCNA2	hsa890
	Down-regulation	Expression	CCNB1	hsa891
	Up-regulation	Phosphorylation	CDK1	hsa983
	Down-regulation	Phosphorylation	CDK2	hsa1017
	Up-regulation	Expression	CDKN2D	hsa1032
	Up-regulation	Expression	H3C14	hsa126961
	Up-regulation	Expression	HRH4	hsa59340
	Down-regulation	Expression	PSMD9	hsa5715
	Down-regulation	Phosphorylation	RICTOR	hsa253260
	Up-regulation	Phosphorylation	RPTOR	hsa57521
In Vitro Model	RT-112	Bladder carcinoma	Homo sapiens (Human)	CVCL_1670
	UM-UC-3	Bladder carcinoma	Homo sapiens (Human)	CVCL_1783
	TCCSUP	Bladder carcinoma	Homo sapiens (Human)	CVCL_1738
Result	The addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

Pair Name	Piceatannol, Everolimus
Partner Name	Piceatannol
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Phosphorylation	BECN1	hsa8678
	Down-regulation	Expression	SQSTM1	hsa8878
In Vitro Model	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
In Vivo Model	2×10⁶ SGC7901 cells were resuspended in phosphate-buffered saline (PBS) containing 50% Matrigel and engrafted subcutaneously into each flank of the mice.
Result	The findings of this study strongly support the application of combinatorial piceatannol and everolimus therapy in future clinical trials for gastric cancer patients.

Pair Name	Genipin, Everolimus
Partner Name	Genipin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Proliferation
Gene Regulation	Up-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	BECN1	hsa8678
	Up-regulation	Expression	MTOR	hsa2475
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	UCP2	hsa7351
In Vitro Model	PaCa-44	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_7087
	PaCa-3	Pancreatic carcinoma	Homo sapiens (Human)	CVCL_4011
	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0428
	T3M-4	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_4056
In Vivo Model	PaCa44 cells (1×10⁶ cells/mice) were s.c. injected into the dorsal flank of six nude female mice for each condition (5 weeks of age; Charles River Laboratories, Inc.).
Result	These results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation and support the combined inhibition of UCP2 and of Akt/mTOR pathway as a novel therapeutic strategy in the treatment of pancreatic adenocarcinoma.

Pair Name	Fangchinoline, Everolimus
Partner Name	Fangchinoline
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
	Up-regulation	Expression	DDIT3	hsa1649
	Down-regulation	Phosphorylation	EIF4EBP1	hsa1978
	Up-regulation	Expression	HES1	hsa3280
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Up-regulation	Expression	MYC	hsa4609
	Up-regulation	Expression	NOTCH1	hsa4851
	Up-regulation	Expression	NOTCH3	hsa4854
	Up-regulation	Cleavage	PARP1	hsa142
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	NCI-H1299	Lung large cell carcinoma	Homo sapiens (Human)	CVCL_0060
	NCI-H358	Minimally invasive lung adenocarcinoma	Homo sapiens (Human)	CVCL_1559
	HCC827	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_2063
	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
Result	Firstly link CHOP to Notch 3/c-MYC axis-dependent apoptosis and provide the Notch 3/c-MYC/CHOP activation as a promising strategy for mTOR-targeted combination therapy in lung cancer treatment.