NPASS Compound

Structure

NPC473249 OpenBabel07101719132D 44 45 0 0 1 0 0 0 0 0999 V2000 1.9448 3.4262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5357 -0.8719 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2463 4.6511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7533 3.6724 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7414 0.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6074 1.7428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8513 2.8858 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5360 4.7135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0936 0.8036 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6942 0.3601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3363 1.3489 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0093 1.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8754 1.7428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3489 2.3363 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7068 3.3251 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5327 3.4424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4113 -0.2572 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1061 2.8815 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1773 0.0617 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9874 3.6852 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9762 3.0431 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4113 1.7428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5452 0.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2773 0.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3987 1.9424 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1899 3.6235 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2773 1.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3939 3.7476 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5452 1.2428 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2746 2.5262 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5936 -0.0624 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3646 3.8723 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2982 4.2306 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1433 1.7428 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.7414 1.2428 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1433 -0.2572 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3415 4.7462 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3208 1.7428 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6459 -1.0610 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5875 4.5016 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3973 1.9948 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5483 4.5570 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2082 2.8846 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 19 1 0 0 0 0 4 21 1 0 0 0 0 5 36 1 0 0 0 0 6 36 1 0 0 0 0 7 42 1 0 0 0 0 8 43 1 0 0 0 0 9 10 1 0 0 0 0 9 11 2 0 0 0 0 10 19 2 0 0 0 0 11 25 1 0 0 0 0 12 13 1 0 0 0 0 12 34 1 0 0 0 0 13 36 1 0 0 0 0 14 18 1 0 0 0 0 14 22 1 0 0 0 0 15 18 1 0 0 0 0 15 26 1 0 0 0 0 16 20 1 0 0 0 0 16 21 2 0 0 0 0 17 23 2 0 0 0 0 17 24 1 0 0 0 0 18 1 1 6 0 0 0 19 31 1 0 0 0 0 20 3 1 6 0 0 0 20 28 1 0 0 0 0 21 30 1 0 0 0 0 22 27 2 0 0 0 0 22 29 1 0 0 0 0 23 29 1 0 0 0 0 23 35 1 0 0 0 0 24 27 1 0 0 0 0 24 37 2 0 0 0 0 25 30 1 0 0 0 0 25 42 1 6 0 0 0 26 28 1 0 0 0 0 26 43 1 1 0 0 0 27 34 1 0 0 0 0 28 38 1 1 0 0 0 29 39 2 0 0 0 0 30 44 1 1 0 0 0 31 35 2 3 0 0 0 31 40 1 0 0 0 0 32 33 2 0 0 0 0 32 41 1 0 0 0 0 32 44 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	616.35
Volume:	635.496
LogP:	2.737
LogD:	2.392
LogS:	-2.914
# Rotatable Bonds:	7
TPSA:	176.17
# H-Bond Aceptor:	12
# H-Bond Donor:	6
# Rings:	2
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.137
Synthetic Accessibility Score:	6.428
Fsp3:	0.531
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.07
MDCK Permeability:	5.050044637755491e-05
Pgp-inhibitor:	0.756
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.98
20% Bioavailability (F20%):	0.118
30% Bioavailability (F30%):	0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.567
Plasma Protein Binding (PPB):	93.02706146240234%
Volume Distribution (VD):	1.301
Pgp-substrate:	5.004883766174316%

ADMET: Metabolism

CYP1A2-inhibitor:	0.019
CYP1A2-substrate:	0.093
CYP2C19-inhibitor:	0.01
CYP2C19-substrate:	0.458
CYP2C9-inhibitor:	0.004
CYP2C9-substrate:	0.132
CYP2D6-inhibitor:	0.038
CYP2D6-substrate:	0.31
CYP3A4-inhibitor:	0.046
CYP3A4-substrate:	0.77

ADMET: Excretion

Clearance (CL):	9.246
Half-life (T1/2):	0.096

ADMET: Toxicity

hERG Blockers:	0.512
Human Hepatotoxicity (H-HT):	0.97
Drug-inuced Liver Injury (DILI):	0.949
AMES Toxicity:	0.544
Rat Oral Acute Toxicity:	0.954
Maximum Recommended Daily Dose:	0.933
Skin Sensitization:	0.882
Carcinogencity:	0.239
Eye Corrosion:	0.003
Eye Irritation:	0.004
Respiratory Toxicity:	0.96

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC473249

Natural Product ID:	NPC473249
*Common Name:**	Alvespimycin
IUPAC Name:	[(3R,5S,6R,7S,8E,10S,11S,12Z,14E)-21-[2-(dimethylamino)ethylamino]-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate
Synonyms:	Alvespimycin
Standard InCHIKey:	KUFRQPKVAWMTJO-LMZWQJSESA-N
Standard InCHI:	InChI=1S/C32H48N4O8/c1-18-14-22-27(34-12-13-36(5)6)24(37)17-23(29(22)39)35-31(40)19(2)10-9-11-25(42-7)30(44-32(33)41)21(4)16-20(3)28(38)26(15-18)43-8/h9-11,16-18,20,25-26,28,30,34,38H,12-15H2,1-8H3,(H2,33,41)(H,35,40)/b11-9-,19-10+,21-16+/t18-,20+,25+,26+,28-,30+/m1/s1
SMILES:	CO[C@H]1C[C@H](C)CC2=C(NCCN(C)C)C(=O)C=C(C2=O)N=C(O)/C(=C/C=C[C@@H]([C@H](/C(=C/[C@@H]([C@H]1O)C)/C)OC(=N)O)OC)/C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL383824
PubChem CID:	5288674
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000064] Macrolactams

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	n.a.	seed	n.a.	DOI[10.1016/S0031-9422(00)97029-8]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	seeds	n.a.	n.a.	PMID[18359631]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	seeds	n.a.	n.a.	PMID[18603435]
NPO2578	Morus sp.	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	PMID[19072214]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[20469887]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[25710081]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3069958]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	seed	n.a.	PMID[8759164]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2578	Morus sp.	Species	Sulidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21707	Trichosanthes kirilowii	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
EC50	9
GI50	2
IC50	51
Kd	5
Ki	2
Others	27

Activity Type	# Activity
Cell Line	28
CELL-LINE	2
Individual Protein	14
NON-MOLECULAR	5
Organism	14
Others	5
Protein Family	20
SINGLE PROTEIN	2
Subcellular	2
Tissue	8

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT134	Cell Line	SK-BR-3	Homo sapiens	IC50	=	24.0	nM	PMID[507746]
NPT4500	Individual Protein	Heat shock protein 90 beta	Canis lupus familiaris	EC50	=	65.0	nM	PMID[507747]
NPT146	Cell Line	SK-OV-3	Homo sapiens	GI50	=	32.0	nM	PMID[507747]
NPT134	Cell Line	SK-BR-3	Homo sapiens	GI50	=	29.0	nM	PMID[507747]
NPT196	Cell Line	AGS	Homo sapiens	IC50	=	16000.0	nM	PMID[507748]
NPT196	Cell Line	AGS	Homo sapiens	IC50	=	16000.0	nM	PMID[507749]
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	2060.0	nM	PMID[507749]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	IC50	=	5.8	nM	PMID[507750]
NPT1383	Cell Line	A2058	Homo sapiens	IC50	=	2.1	nM	PMID[507750]
NPT134	Cell Line	SK-BR-3	Homo sapiens	IC50	=	24.0	nM	PMID[507751]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	Kd	=	500.0	nM	PMID[507751]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	230.0	nM	PMID[507751]
NPT146	Cell Line	SK-OV-3	Homo sapiens	IC50	=	220.0	nM	PMID[507751]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	68.0	nM	PMID[507751]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	IC50	=	540.0	nM	PMID[507751]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	IC50	=	2500.0	nM	PMID[507751]
NPT134	Cell Line	SK-BR-3	Homo sapiens	IC50	=	58.0	nM	PMID[507752]
NPT146	Cell Line	SK-OV-3	Homo sapiens	IC50	=	122.0	nM	PMID[507752]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	57.0	nM	PMID[507752]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	71.0	nM	PMID[507752]
NPT2335	Cell Line	NCI-H596		IC50	=	1100.0	nM	PMID[507752]
NPT134	Cell Line	SK-BR-3	Homo sapiens	IC50	=	230.0	nM	PMID[507752]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	862.0	nM	PMID[507752]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	IC50	=	24.0	nM	PMID[507753]
NPT211	Individual Protein	Hypoxia-inducible factor 1 alpha	Homo sapiens	IC50	=	57.2	nM	PMID[507754]
NPT211	Individual Protein	Hypoxia-inducible factor 1 alpha	Homo sapiens	IC50	=	57.0	nM	PMID[507757]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	50.0	nM	PMID[507758]
NPT1383	Cell Line	A2058	Homo sapiens	TGI	=	34.0	%	PMID[507761]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	780.0	nM	PMID[507764]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	390.0	nM	PMID[507764]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	IC50	=	930.0	nM	PMID[507764]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	IC50	=	1410.0	nM	PMID[507765]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	IC50	=	90.0	nM	PMID[507765]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	800.0	nM	PMID[507765]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	1210.0	nM	PMID[507765]
NPT1429	Individual Protein	Heat shock protein HSP 90-beta	Homo sapiens	Inhibition	=	88.31	%	PMID[507765]
NPT3377	Cell Line	PC-9		IC50	=	10.0	nM	PMID[507770]
NPT918	Individual Protein	Heat shock protein HSP 90-alpha	Homo sapiens	Kd	=	500.0	nM	PMID[507746]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	14.0	nM	PMID[507747]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	4.0	nM	PMID[507747]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	46.0	nM	PMID[507747]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	8.0	nM	PMID[507747]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	62.0	nM	PMID[507747]
NPT21802	PROTEIN FAMILY	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	36.0	nM	PMID[507748]
NPT21802	PROTEIN FAMILY	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	61.0	nM	PMID[507748]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	50000.0	nM	PMID[507748]
NPT2	Others	Unspecified		IC50	=	150.0	nM	PMID[507749]
NPT21802	PROTEIN FAMILY	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	=	3.6	nM	PMID[507749]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	17.6	nM	PMID[507750]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	4.5	nM	PMID[507750]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	24.3	nM	PMID[507750]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	EC50	=	7.9	nM	PMID[507750]
NPT918	Individual Protein	Heat shock protein HSP 90-alpha	Homo sapiens	Kd	=	500.0	nM	PMID[507752]
NPT918	Individual Protein	Heat shock protein HSP 90-alpha	Homo sapiens	Kd	=	87.0	nM	PMID[507752]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	1600.0	nM	PMID[507752]
NPT20904	CELL-LINE	Hep 3B2	Homo sapiens	IC50	=	79.5	nM	PMID[507754]
NPT21802	PROTEIN FAMILY	Hypoxia inducible factors; HIF-1-alpha, HIF-2-alpha	Homo sapiens	IC50	>	30000.0	nM	PMID[507754]
NPT433	Subcellular	Liver microsomes	Homo sapiens	CLH	<	3.0	uL/min	PMID[507755]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	100.0	nM	PMID[507755]
NPT2	Others	Unspecified		Ki	=	250.0	nM	PMID[507755]
NPT35	Others	n.a.		T1/2	=	0.4333	hr	PMID[507756]
NPT1016	Organism	Canis familiaris	Canis lupus familiaris	MTD	=	8.0	mg/m2	PMID[507756]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	MTD	=	12.0	mg/m2	PMID[507756]
NPT20904	CELL-LINE	Hep 3B2	Homo sapiens	IC50	=	79.0	nM	PMID[507757]
NPT2	Others	Unspecified		Kd	=	210.0	nM	PMID[507758]
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	EC50	=	1.2	nM	PMID[507760]
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	EC50	=	3.1	nM	PMID[507760]
NPT191	Organism	Hepatitis C virus	Hepatitis C virus	Ratio IC50	=	3.0	n.a.	PMID[507760]
NPT918	Individual Protein	Heat shock protein HSP 90-alpha	Homo sapiens	Ki	=	680.0	nM	PMID[507761]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	100.0	nM	PMID[507761]
NPT433	Subcellular	Liver microsomes	Homo sapiens	CL	=	12.3	mL.min-1.g-1	PMID[507761]
NPT32	Organism	Mus musculus	Mus musculus	MTD	=	10.0	mg kg-1	PMID[507761]
NPT32	Organism	Mus musculus	Mus musculus	Inhibition	=	84.0	%	PMID[507763]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	1340.0	nM	PMID[507764]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	3110.0	nM	PMID[507765]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	170.0	nM	PMID[507765]
NPT605	Organism	Homo sapiens	Homo sapiens	T1/2	=	16.0	hr	PMID[507767]
NPT605	Organism	Homo sapiens	Homo sapiens	CL	=	7.4	L/hr	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Stability	=	24.0	%	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Km	=	6610.0	nM	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Km	=	7830.0	nM	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Inhibition	=	83.0	%	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Inhibition	=	81.0	%	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Inhibition	=	79.0	%	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Inhibition	=	77.0	%	PMID[507767]
NPT626	Tissue	Liver microsome	Homo sapiens	Inhibition	=	75.0	%	PMID[507767]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.7	%	PMID[507769]
NPT2	Others	Unspecified		IC50	=	10.0	nM	PMID[507770]
NPT2264	Protein Family	Heat shock protein HSP90	Homo sapiens	IC50	=	24.0	nM	PMID[507770]
NPT918	Individual Protein	Heat shock protein HSP 90-alpha	Homo sapiens	IC50	=	919.0	nM	PMID[507771]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	12.91	%	PMID[507772]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	10.6	%	PMID[507773]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.32	%	PMID[507774]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.33	%	PMID[507775]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC473249 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	86
0.1-0.2	490
0.2-0.3	3072
0.3-0.4	22581
0.4-0.5	13781
0.5-0.6	2523
0.6-0.7	149
0.7-0.8	7
0.8-0.85	6
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.843	Intermediate Similarity	NPC59751
0.843	Intermediate Similarity	NPC27413
0.843	Intermediate Similarity	NPC271621
0.8182	Intermediate Similarity	NPC5485
0.813	Intermediate Similarity	NPC316325
0.8049	Intermediate Similarity	NPC7905
0.8049	Intermediate Similarity	NPC315652
0.8016	Intermediate Similarity	NPC315915
0.7937	Intermediate Similarity	NPC473808
0.7778	Intermediate Similarity	NPC296361
0.7174	Intermediate Similarity	NPC314361
0.7143	Intermediate Similarity	NPC133729
0.7097	Intermediate Similarity	NPC472616
0.704	Intermediate Similarity	NPC472615
0.7	Intermediate Similarity	NPC103391
0.7	Intermediate Similarity	NPC471645
0.7	Intermediate Similarity	NPC472536
0.686	Remote Similarity	NPC205546
0.686	Remote Similarity	NPC233273
0.686	Remote Similarity	NPC189764
0.686	Remote Similarity	NPC50902
0.685	Remote Similarity	NPC251330
0.6767	Remote Similarity	NPC475642
0.6667	Remote Similarity	NPC175614
0.6641	Remote Similarity	NPC271269
0.6641	Remote Similarity	NPC154601
0.6623	Remote Similarity	NPC135121
0.6591	Remote Similarity	NPC469865
0.6587	Remote Similarity	NPC316250
0.6569	Remote Similarity	NPC475383
0.6569	Remote Similarity	NPC156379
0.6565	Remote Similarity	NPC477997
0.6538	Remote Similarity	NPC140251
0.6538	Remote Similarity	NPC307903
0.6519	Remote Similarity	NPC476190
0.6515	Remote Similarity	NPC21713
0.6515	Remote Similarity	NPC475608
0.649	Remote Similarity	NPC201244
0.649	Remote Similarity	NPC477217
0.6489	Remote Similarity	NPC175585
0.6486	Remote Similarity	NPC315848
0.6486	Remote Similarity	NPC315210
0.6475	Remote Similarity	NPC315783
0.6471	Remote Similarity	NPC80738
0.6449	Remote Similarity	NPC160688
0.6449	Remote Similarity	NPC314293
0.6429	Remote Similarity	NPC470654
0.6429	Remote Similarity	NPC470650
0.6429	Remote Similarity	NPC470653
0.6423	Remote Similarity	NPC241050
0.6417	Remote Similarity	NPC472614
0.6412	Remote Similarity	NPC207820
0.6408	Remote Similarity	NPC477793
0.6408	Remote Similarity	NPC329919
0.6395	Remote Similarity	NPC230889
0.6377	Remote Similarity	NPC314482
0.6364	Remote Similarity	NPC473578
0.6364	Remote Similarity	NPC298484
0.634	Remote Similarity	NPC471674
0.634	Remote Similarity	NPC201899
0.6336	Remote Similarity	NPC315531
0.632	Remote Similarity	NPC469739
0.6316	Remote Similarity	NPC122926
0.6316	Remote Similarity	NPC113012
0.6312	Remote Similarity	NPC469494
0.6304	Remote Similarity	NPC313802
0.6304	Remote Similarity	NPC314268
0.6304	Remote Similarity	NPC477515
0.6304	Remote Similarity	NPC67917
0.6288	Remote Similarity	NPC474099
0.6288	Remote Similarity	NPC475150
0.6277	Remote Similarity	NPC6531
0.6275	Remote Similarity	NPC316249
0.6269	Remote Similarity	NPC170375
0.6269	Remote Similarity	NPC29501
0.626	Remote Similarity	NPC236322
0.626	Remote Similarity	NPC201128
0.6259	Remote Similarity	NPC139867
0.6241	Remote Similarity	NPC314629
0.6241	Remote Similarity	NPC16709
0.6241	Remote Similarity	NPC24389
0.6231	Remote Similarity	NPC474827
0.6231	Remote Similarity	NPC199831
0.6231	Remote Similarity	NPC474563
0.6231	Remote Similarity	NPC68001
0.6231	Remote Similarity	NPC474828
0.6224	Remote Similarity	NPC475610
0.6222	Remote Similarity	NPC476269
0.622	Remote Similarity	NPC476344
0.6204	Remote Similarity	NPC296043
0.6204	Remote Similarity	NPC30196
0.6202	Remote Similarity	NPC175531
0.6202	Remote Similarity	NPC34193
0.6194	Remote Similarity	NPC469603
0.619	Remote Similarity	NPC78189
0.619	Remote Similarity	NPC150041
0.6183	Remote Similarity	NPC469958
0.617	Remote Similarity	NPC273185
0.6165	Remote Similarity	NPC24596
0.6164	Remote Similarity	NPC120335
0.616	Remote Similarity	NPC472613
0.6159	Remote Similarity	NPC329216
0.6154	Remote Similarity	NPC313173
0.6143	Remote Similarity	NPC477143
0.6143	Remote Similarity	NPC470652
0.6143	Remote Similarity	NPC477140
0.6142	Remote Similarity	NPC195645
0.6142	Remote Similarity	NPC165332
0.6142	Remote Similarity	NPC180722
0.6138	Remote Similarity	NPC110294
0.6127	Remote Similarity	NPC318445
0.6127	Remote Similarity	NPC316133
0.6127	Remote Similarity	NPC66855
0.6111	Remote Similarity	NPC262845
0.6111	Remote Similarity	NPC68293
0.6111	Remote Similarity	NPC5418
0.6107	Remote Similarity	NPC55336
0.6103	Remote Similarity	NPC1111
0.6103	Remote Similarity	NPC261750
0.6103	Remote Similarity	NPC60432
0.6099	Remote Similarity	NPC469515
0.6099	Remote Similarity	NPC315188
0.6094	Remote Similarity	NPC472162
0.609	Remote Similarity	NPC315426
0.6084	Remote Similarity	NPC160493
0.6078	Remote Similarity	NPC470886
0.6077	Remote Similarity	NPC77703
0.6077	Remote Similarity	NPC313234
0.6076	Remote Similarity	NPC7817
0.6076	Remote Similarity	NPC475168
0.6074	Remote Similarity	NPC476290
0.6066	Remote Similarity	NPC316426
0.6066	Remote Similarity	NPC315395
0.6061	Remote Similarity	NPC477001
0.6061	Remote Similarity	NPC477000
0.6061	Remote Similarity	NPC205176
0.6054	Remote Similarity	NPC316401
0.6047	Remote Similarity	NPC161855
0.604	Remote Similarity	NPC99864
0.6033	Remote Similarity	NPC161670
0.6031	Remote Similarity	NPC469598
0.6031	Remote Similarity	NPC473596
0.6027	Remote Similarity	NPC315387
0.6027	Remote Similarity	NPC316205
0.6016	Remote Similarity	NPC475503
0.6015	Remote Similarity	NPC185929
0.6015	Remote Similarity	NPC230677
0.6014	Remote Similarity	NPC133089
0.6013	Remote Similarity	NPC300912
0.6013	Remote Similarity	NPC202166
0.6013	Remote Similarity	NPC473261
0.6013	Remote Similarity	NPC473262
0.6	Remote Similarity	NPC314282
0.5987	Remote Similarity	NPC130714
0.5985	Remote Similarity	NPC469895
0.5984	Remote Similarity	NPC116930
0.5973	Remote Similarity	NPC120420
0.5972	Remote Similarity	NPC314512
0.5972	Remote Similarity	NPC314451
0.5972	Remote Similarity	NPC313333
0.5972	Remote Similarity	NPC313342
0.597	Remote Similarity	NPC467022
0.5969	Remote Similarity	NPC265662
0.5968	Remote Similarity	NPC316186
0.5963	Remote Similarity	NPC470902
0.596	Remote Similarity	NPC473683
0.5952	Remote Similarity	NPC472010
0.5946	Remote Similarity	NPC315011
0.5944	Remote Similarity	NPC190663
0.594	Remote Similarity	NPC74035
0.5933	Remote Similarity	NPC471256
0.5931	Remote Similarity	NPC309525
0.5931	Remote Similarity	NPC471263
0.5923	Remote Similarity	NPC203627
0.5912	Remote Similarity	NPC2501
0.5909	Remote Similarity	NPC128501
0.5909	Remote Similarity	NPC226509
0.5909	Remote Similarity	NPC474244
0.5909	Remote Similarity	NPC152718
0.5906	Remote Similarity	NPC477462
0.5904	Remote Similarity	NPC471052
0.5904	Remote Similarity	NPC471051
0.5904	Remote Similarity	NPC471053
0.5903	Remote Similarity	NPC50520
0.5901	Remote Similarity	NPC473341
0.5896	Remote Similarity	NPC472433
0.5891	Remote Similarity	NPC473291
0.589	Remote Similarity	NPC317654
0.589	Remote Similarity	NPC96010
0.5882	Remote Similarity	NPC133625
0.5882	Remote Similarity	NPC314854
0.5882	Remote Similarity	NPC127741
0.5882	Remote Similarity	NPC313911
0.5879	Remote Similarity	NPC114806
0.5879	Remote Similarity	NPC469901
0.5878	Remote Similarity	NPC316730
0.587	Remote Similarity	NPC314550
0.5868	Remote Similarity	NPC63931
0.5865	Remote Similarity	NPC476877
0.5862	Remote Similarity	NPC204639

Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC473249 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	80
0.1-0.2	250
0.2-0.3	1591
0.3-0.4	4665
0.4-0.5	2350
0.5-0.6	197
0.6-0.7	9
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7746	Phase 1
1.0	High Similarity	NPD7747	Phase 1
0.9487	High Similarity	NPD7624	Clinical (unspecified phase)
0.9487	High Similarity	NPD7623	Phase 3
0.9237	High Similarity	NPD7739	Clinical (unspecified phase)
0.8793	High Similarity	NPD7116	Clinical (unspecified phase)
0.813	Intermediate Similarity	NPD7500	Approved
0.808	Intermediate Similarity	NPD7299	Clinical (unspecified phase)
0.6619	Remote Similarity	NPD8273	Phase 1
0.6475	Remote Similarity	NPD7829	Approved
0.6475	Remote Similarity	NPD7830	Approved
0.635	Remote Similarity	NPD7641	Discontinued
0.6331	Remote Similarity	NPD8444	Approved
0.6277	Remote Similarity	NPD7505	Discontinued
0.6269	Remote Similarity	NPD7601	Clinical (unspecified phase)
0.6259	Remote Similarity	NPD1689	Approved
0.6225	Remote Similarity	NPD6077	Discontinued
0.6142	Remote Similarity	NPD7839	Suspended
0.6127	Remote Similarity	NPD7642	Approved
0.6074	Remote Similarity	NPD6421	Discontinued
0.6071	Remote Similarity	NPD2132	Phase 3
0.6042	Remote Similarity	NPD8451	Approved
0.6042	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.604	Remote Similarity	NPD8415	Approved
0.6	Remote Similarity	NPD8448	Approved
0.6	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.6	Remote Similarity	NPD6681	Discovery
0.6	Remote Similarity	NPD6413	Approved
0.5986	Remote Similarity	NPD8390	Approved
0.5986	Remote Similarity	NPD8392	Approved
0.5986	Remote Similarity	NPD8391	Approved
0.5986	Remote Similarity	NPD6914	Discontinued
0.5985	Remote Similarity	NPD2259	Approved
0.5985	Remote Similarity	NPD2258	Approved
0.5972	Remote Similarity	NPD8340	Approved
0.5972	Remote Similarity	NPD8299	Approved
0.5972	Remote Similarity	NPD8341	Approved
0.5972	Remote Similarity	NPD8342	Approved
0.5946	Remote Similarity	NPD7260	Phase 2
0.5946	Remote Similarity	NPD2101	Approved
0.5923	Remote Similarity	NPD8029	Clinical (unspecified phase)
0.589	Remote Similarity	NPD8074	Phase 3
0.5844	Remote Similarity	NPD6852	Discontinued
0.5827	Remote Similarity	NPD1376	Discontinued
0.58	Remote Similarity	NPD6845	Suspended
0.5762	Remote Similarity	NPD6919	Clinical (unspecified phase)
0.5748	Remote Similarity	NPD6698	Approved
0.5748	Remote Similarity	NPD46	Approved
0.5748	Remote Similarity	NPD7838	Discovery
0.5725	Remote Similarity	NPD6420	Discontinued
0.5724	Remote Similarity	NPD2838	Clinical (unspecified phase)
0.5703	Remote Similarity	NPD7983	Approved
0.5677	Remote Similarity	NPD3528	Clinical (unspecified phase)
0.5605	Remote Similarity	NPD8384	Approved

Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data