NPASS Compound

Natural Product: NPC167606

Natural Product ID	NPC167606
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Withaferin A
IUPAC Name	n.a.
Synonyms	NSC-101088
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1221986
PubChem CID	49864510
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 72 77 0 0 0 0 0 0 0 0999 V2000 7.7335 1.7059 1.4301 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1528 2.0923 0.2505 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8211 1.4884 0.0452 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2942 0.6761 0.9258 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9800 0.2878 2.1950 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9340 0.1356 0.6878 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7528 -0.1119 -0.7857 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8499 1.1692 -1.3956 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0810 1.7846 -1.2150 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6096 2.5684 -2.0336 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4574 -0.8286 -1.0745 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3171 -0.0741 -0.6313 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2457 1.2625 -1.3377 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2353 1.5349 -1.5440 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8461 0.6530 -0.5318 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0570 -0.6534 -0.7274 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3929 -1.3414 -1.9865 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4393 -1.4859 0.4630 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9246 -1.7566 0.4930 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7657 -0.5437 0.3952 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3157 0.4738 -0.6114 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9258 1.7958 -0.1965 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3333 1.6880 0.2595 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9585 0.4508 0.4855 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2117 -0.8103 0.1147 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4146 -1.0132 -1.3970 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7747 -2.0112 0.7397 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1110 -3.0553 0.8304 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1225 -2.0098 1.2673 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6374 -0.8852 1.7607 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7907 0.3086 1.7401 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.5160 1.4911 1.8758 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3634 1.2734 -0.5469 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6245 -2.2343 -0.5763 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6463 1.3000 1.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0663 3.2185 0.2481 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8215 1.8308 -0.5994 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9027 -0.3186 2.0134 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3073 -0.4346 2.7428 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1138 1.1166 2.8996 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2086 0.8897 1.0708 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7659 -0.7745 1.2986 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6162 -0.7805 -1.0902 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4350 -0.9267 -2.2053 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4322 0.1828 0.4670 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7755 1.2359 -2.3195 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6384 2.0907 -0.7297 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5001 1.3041 -2.5889 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4913 2.5884 -1.3069 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5939 1.0398 0.4773 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8867 -2.3450 -1.8390 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1768 -0.7498 -2.5299 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4512 -1.4223 -2.7088 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1359 -0.8970 1.3748 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0793 -2.4432 0.5361 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0888 -2.1964 1.5232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1160 -2.5506 -0.2262 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7345 -0.0382 1.4065 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6922 0.2838 -1.6402 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3124 2.1446 0.6836 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8031 2.5356 -1.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6328 2.5684 0.9089 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5566 -1.5468 -1.8522 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6765 -0.0626 -1.8993 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2992 -1.6777 -1.5689 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7492 -2.9135 1.2777 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6286 -0.8368 2.1606 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0620 0.2790 2.5896 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9811 2.1517 2.3817 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7116 -2.3312 0.5042 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5796 -2.6244 -1.0098 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8485 -2.9156 -1.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 7 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 6 25 27 1 0 27 28 2 0 27 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 24 33 1 6 11 34 1 0 9 3 1 0 16 12 1 0 25 20 1 0 21 15 1 0 33 23 1 0 31 24 1 0 1 35 1 0 2 36 1 0 2 37 1 0 5 38 1 0 5 39 1 0 5 40 1 0 6 41 1 0 6 42 1 0 7 43 1 6 11 44 1 6 12 45 1 1 13 46 1 0 13 47 1 0 14 48 1 0 14 49 1 0 15 50 1 1 17 51 1 0 17 52 1 0 17 53 1 0 18 54 1 0 18 55 1 0 19 56 1 0 19 57 1 0 20 58 1 1 21 59 1 6 22 60 1 0 22 61 1 0 23 62 1 1 26 63 1 0 26 64 1 0 26 65 1 0 29 66 1 0 30 67 1 0 31 68 1 1 32 69 1 0 34 70 1 0 34 71 1 0 34 72 1 0 M END

Standard InCHIKey	DBRXOUCRJQVYJQ-BZMBVROXSA-N
Standard InCHI	InChI=1S/C28H38O6/c1-14-11-21(33-25(32)17(14)13-29)15(2)18-5-6-19-16-12-24-28(34-24)23(31)8-7-22(30)27(28,4)20(16)9-10-26(18,19)3/h7-8,15-16,18-21,23-24,29,31H,5-6,9-13H2,1-4H3/t15-,16-,18+,19-,20-,21-,23-,24+,26+,27-,28+/m0/s1
SMILES	OCC1=C(C)C[C@H](OC1=O)[C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2C[C@@H]2[C@]3([C@]1(C)C(=O)C=C[C@@H]3O)O2)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.27	Volume:	483.701 ? Van der Waals volume.
Dense:	0.972	LogP:	2.763 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.134 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.227 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	30.0
TPSA:	96.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.485	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.721	Fsp³:	0.786
MCE-18:	141.96 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.596	Fluc inhibitor:	0.099 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.166	Promiscuous compounds:	0.564

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.165	MDCK Permeability:	-4.975
Pgp-inhibitor:	0.77	Pgp-substrate:	0.006
PAMPA:	0.019 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.001
20% Bioavailability (F20%):	0.009	30% Bioavailability (F30%):	0.496
50% Bioavailability (F50%):	0.877

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.085	MRP1:	0.304
Plasma Protein Binding (PPB):	77.846%	Volume Distribution (VD):	-0.124
Fu:	19.004% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.045
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.222	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.006	CYP3A4-substrate:	0.984
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.983
HLM stability:	0.47 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

9.291

Half-life (T1/2):

1.37

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.177
Human Hepatotoxicity (H-HT):	0.615	Drug-induced Liver Injury (DILI):	0.749
AMES Toxicity:	0.869	Rat Oral Acute Toxicity:	0.342
Maximum Recommended Daily Dose:	0.766	Skin Sensitization:	0.999
Carcinogencity:	0.987	Eye Corrosion:	0.022
Eye Irritation:	0.724	Respiratory Toxicity:	0.851
Drug-induced Neurotoxicity:	0.12	Ototoxicity:	0.527
Hematotoxicity:	0.601	Drug-induced Nephrotoxicity:	0.861
Genotoxicity:	0.895	RPMI-8226 Immunitoxicity:	0.104
A549 Cytotoxicity:	0.096	Hek293 Cytotoxicity:	0.648
BCF:	1.515 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.114 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.886 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.169 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11240-013-0297-z]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/0031-9422(75)85035-7]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.indcrop.2015.06.012]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	roots	n.a.	n.a.	PMID[17190461]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19056281]
NPO7729	Vassobia breviflora	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20726569]
NPO14874	Physalis longifolia	Species	Solanaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[22098611]
NPO14874	Physalis longifolia	Species	Solanaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[22098611]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22705001]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24079846]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26169123]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30776236]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36350950]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15698	Withania somnifera	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14874	Physalis longifolia	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20281	Withania aristata	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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	Organism Name	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
Activity	12
FC	3
IC50	45
GI50	1
Inhibition	2
Ratio IC50	2
MTD	1

Activity Type	# Activity
Individual protein	3
Cell line	37
Organism	1
Others	10
Non-molecular	15

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT979	Individual protein	Caspase-3	Homo sapiens	FC	=	1.0	n.a.	PMID[21044847]
NPT4377	Individual protein	Heat shock 70 kDa protein 6	Homo sapiens	FC	=	1.35	n.a.	PMID[18232640]
NPT728	Individual protein	Serine/threonine-protein kinase AKT	Homo sapiens	Activity	=	2.5	uM	PMID[24273638]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	0.06	ug.mL-1	PMID[22691154]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	0.05	ug.mL-1	PMID[18183025]
NPT81	Cell line	A549	Homo sapiens	IC50	=	0.02	ug.mL-1	PMID[17850214]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	0.02	ug.mL-1	PMID[17850214]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	0.07	ug.mL-1	PMID[18183025]
NPT83	Cell line	MCF7	Homo sapiens	Inhibition	=	50.0	%	PMID[25232969]
NPT169	Cell line	B16-F10	Mus musculus	IC50	=	290.0	nM	PMID[22931472]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	=	4000.0	nM	PMID[26636180]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	3000.0	nM	PMID[25682561]
NPT81	Cell line	A549	Homo sapiens	IC50	=	6600.0	nM	PMID[23398362]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	2300.0	nM	PMID[26046820]
NPT81	Cell line	A549	Homo sapiens	IC50	=	1500.0	nM	PMID[17190457]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	3600.0	nM	PMID[26848627]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	600.0	nM	PMID[25682561]
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	1300.0	nM	DrugMatrix in vivo data: Pathology
NPT189	Cell line	Vero	Chlorocebus aethiops	IC50	=	1700.0	nM	PMID[19053514]
NPT189	Cell line	Vero	Chlorocebus aethiops	Ratio IC50	<	1.0	n.a.	PMID[19433554]
NPT171	Cell line	MRC5	Homo sapiens	Ratio IC50	=	0.19	n.a.	PMID[23252848]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	200.0	nM	PMID[19581457]
NPT380	Cell line	U-251	Homo sapiens	IC50	=	690.0	nM	PMID[20550123]
NPT90	Cell line	DU-145	Homo sapiens	Activity	=	24.75	%	PMID[15217282]
NPT90	Cell line	DU-145	Homo sapiens	Activity	=	36.75	%	PMID[26073007]
NPT306	Cell line	PC-3	Homo sapiens	Activity	=	60.7	%	PMID[18183025]
NPT306	Cell line	PC-3	Homo sapiens	Activity	=	62.7	%	PMID[18715034]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	2700.0	nM	PMID[24359277]
NPT170	Cell line	SK-MEL-28	Homo sapiens	IC50	=	1000.0	nM	DOI[10.1007/s00044-011-9808-9]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	540.0	nM	PMID[21377877]
NPT858	Cell line	LNCaP	Homo sapiens	IC50	=	870.0	nM	PMID[17261619]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	410.0	nM	DOI[10.1007/s00044-011-9767-1]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	570.0	nM	PMID[16510283]
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	<	400.0	nM	PMID[16441066]
NPT395	Cell line	SF-268	Homo sapiens	IC50	<	400.0	nM	PubChem BioAssay data set
NPT859	Cell line	HFF	Homo sapiens	IC50	>	6800.0	nM	PMID[12880316]
NPT90	Cell line	DU-145	Homo sapiens	IC50	=	2500.0	nM	PMID[25066952]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	6300.0	nM	PMID[17850214]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	500.0	nM	PMID[9249973]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	1300.0	nM	PMID[18616221]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	620.0	nM	PMID[19056281]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	500.0	nM	PMID[20726569]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	800.0	nM	PMID[23252848]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2000.0	nM	PMID[20726569]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	2200.0	nM	PMID[20726569]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1100.0	nM	PMID[23252848]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	780.0	nM	PMID[24273633]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1000.0	nM	PMID[24273633]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	>	80.0	%	PMID[24625088]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	970.0	nM	PMID[24625088]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	250.0	nM	PMID[24625088]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1600.0	nM	PMID[26169123]
NPT2	Others	Unspecified	n.a.	IC50	=	250.0	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Activity	=	42.0	%	PMID[23891163]
NPT2	Others	Unspecified	n.a.	Activity	=	49.0	%	PMID[23891163]
NPT2	Others	Unspecified	n.a.	Activity	=	34.0	%	PMID[23891163]
NPT2	Others	Unspecified	n.a.	Activity	=	36.0	%	PMID[23891163]
NPT2	Others	Unspecified	n.a.	Activity	=	12.0	%	PMID[21741249]
NPT2	Others	Unspecified	n.a.	Activity	=	8.0	%	PMID[16933872]
NPT2	Others	Unspecified	n.a.	Activity	=	14.8	%	PMID[16933872]
NPT2	Others	Unspecified	n.a.	FC	=	2.1	n.a.	PMID[19124661]
NPT2	Others	Unspecified	n.a.	IC50	=	500.0	nM	PMID[23891163]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	MTD	<=	50.0	mg kg-1	PMID[24625088]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC167606 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	17140
0.1-0.2	27198
0.2-0.3	5310
0.3-0.4	127
0.4-0.5	16
0.5-0.6	39
0.6-0.7	10
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC140055
0.875	High Similarity	NPC286528
0.8485	Intermediate Similarity	NPC709
0.8	Intermediate Similarity	NPC20302
0.7778	Intermediate Similarity	NPC470494
0.7536	Intermediate Similarity	NPC50774
0.75	Intermediate Similarity	NPC312824
0.7429	Intermediate Similarity	NPC470265
0.7391	Intermediate Similarity	NPC243065
0.7368	Intermediate Similarity	NPC3381
0.726	Intermediate Similarity	NPC264954
0.7222	Intermediate Similarity	NPC474370
0.7183	Intermediate Similarity	NPC284915
0.7183	Intermediate Similarity	NPC122056
0.7183	Intermediate Similarity	NPC268530
0.7083	Intermediate Similarity	NPC154491
0.7037	Intermediate Similarity	NPC231240
0.6757	Remote Similarity	NPC159456
0.6579	Remote Similarity	NPC470492
0.6533	Remote Similarity	NPC183580
0.6456	Remote Similarity	NPC120994
0.64	Remote Similarity	NPC609580
0.6316	Remote Similarity	NPC88326
0.6264	Remote Similarity	NPC316915
0.6173	Remote Similarity	NPC203702
0.6133	Remote Similarity	NPC250312
0.6104	Remote Similarity	NPC470493
0.5974	Remote Similarity	NPC473274
0.5949	Remote Similarity	NPC67569
0.5946	Remote Similarity	NPC69291
0.5897	Remote Similarity	NPC4021
0.5867	Remote Similarity	NPC67259
0.5867	Remote Similarity	NPC91034
0.5844	Remote Similarity	NPC270929
0.5844	Remote Similarity	NPC30923
0.5844	Remote Similarity	NPC610236
0.5823	Remote Similarity	NPC153700
0.575	Remote Similarity	NPC251226
0.575	Remote Similarity	NPC8369
0.575	Remote Similarity	NPC600975
0.575	Remote Similarity	NPC602010
0.5696	Remote Similarity	NPC470878
0.5658	Remote Similarity	NPC474315
0.5641	Remote Similarity	NPC156797
0.56	Remote Similarity	NPC220155
0.5584	Remote Similarity	NPC147912
0.5556	Remote Similarity	NPC608655
0.5542	Remote Similarity	NPC23786
0.5542	Remote Similarity	NPC473593
0.55	Remote Similarity	NPC61520
0.55	Remote Similarity	NPC470495
0.5488	Remote Similarity	NPC609769
0.5488	Remote Similarity	NPC610140
0.5432	Remote Similarity	NPC473253
0.5422	Remote Similarity	NPC606886
0.525	Remote Similarity	NPC230513
0.5244	Remote Similarity	NPC8374
0.5244	Remote Similarity	NPC473256
0.5238	Remote Similarity	NPC470880
0.5185	Remote Similarity	NPC186525
0.5185	Remote Similarity	NPC125794
0.5185	Remote Similarity	NPC171401
0.5128	Remote Similarity	NPC285956
0.5122	Remote Similarity	NPC329736
0.5122	Remote Similarity	NPC599946
0.506	Remote Similarity	NPC329671

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC167606 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6299
0.1-0.2	2672
0.2-0.3	177
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7115	Discovery

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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