NPASS Compound

Natural Product: NPC303658

Natural Product ID	NPC303658
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Tryprostatin A
IUPAC Name	(3S,8aS)-3-[[6-methoxy-2-(3-methylbut-2-enyl)-1H-indol-3-yl]methyl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL289159
PubChem CID	9929833
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids 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 55 58 0 0 0 0 0 0 0 0999 V2000 2.9704 6.3435 0.4065 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1947 5.0418 0.8812 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5156 3.9136 0.4682 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5248 3.9085 -0.4660 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9038 2.7116 -0.8102 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2868 1.5406 -0.2120 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2780 1.5283 0.7260 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8950 2.7121 1.0692 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4642 0.2755 1.1560 N 0 0 0 0 0 0 0 0 0 0 0 0 1.6002 -0.5359 0.5055 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8622 0.2236 -0.3449 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2067 -0.2017 -1.2649 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5417 0.1909 -0.6944 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7262 -0.4545 0.5950 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8970 -0.5280 1.1648 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9528 -1.1658 2.3923 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0884 0.0567 0.4955 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9688 -0.1806 -0.9525 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.6863 -0.1850 -1.5578 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5158 -0.4901 -2.7640 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3149 -0.3647 -1.4028 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8747 -1.2902 -0.3385 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3255 -0.6611 0.9229 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5222 -1.9993 0.7220 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1832 -2.6787 -0.4043 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2366 -3.4682 -0.2224 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8999 -4.1518 -1.3635 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7564 -3.6653 1.1496 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9091 6.4347 0.0953 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1849 7.1199 1.1764 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6322 6.4991 -0.4737 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2227 4.8167 -0.9333 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1174 2.7394 -1.5586 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6801 2.7013 1.8135 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1595 -0.0520 1.8779 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1236 0.2984 -2.2589 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2138 -1.2741 -1.4505 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5793 1.3051 -0.5097 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3191 -1.9180 2.6123 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1333 1.1585 0.6129 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4053 -0.7872 -2.4197 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8304 0.6374 -1.3256 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9835 -1.3079 -0.3483 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4309 -2.2867 -0.4971 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1212 -1.4032 1.7150 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0466 0.1051 1.3008 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0128 -2.2760 1.6860 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4636 -2.3421 0.7928 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8121 -2.5395 -1.4073 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9218 -4.4778 -1.0680 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3018 -5.0181 -1.6713 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9997 -3.4076 -2.1861 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9954 -4.0748 1.8421 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1558 -2.7119 1.5887 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6227 -4.3647 1.1377 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 5 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 18 21 1 0 21 22 1 0 22 23 1 0 10 24 1 0 24 25 1 0 25 26 2 3 26 27 1 0 26 28 1 0 8 3 1 0 19 13 1 0 11 6 1 0 23 17 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 5 33 1 0 8 34 1 0 9 35 1 0 12 36 1 0 12 37 1 0 13 38 1 1 16 39 1 0 17 40 1 6 21 41 1 0 21 42 1 0 22 43 1 0 22 44 1 0 23 45 1 0 23 46 1 0 24 47 1 0 24 48 1 0 25 49 1 0 27 50 1 0 27 51 1 0 27 52 1 0 28 53 1 0 28 54 1 0 28 55 1 0 M END

Standard InCHIKey	XNRPVPHNDQHWLJ-PMACEKPBSA-N
Standard InCHI	InChI=1S/C22H27N3O3/c1-13(2)6-9-17-16(15-8-7-14(28-3)11-18(15)23-17)12-19-22(27)25-10-4-5-20(25)21(26)24-19/h6-8,11,19-20,23H,4-5,9-10,12H2,1-3H3,(H,24,26)/t19-,20-/m0/s1
SMILES	COc1ccc2c(c1)[nH]c(c2C[C@@H]1N=C(O)[C@H]2N(C1=O)CCC2)CC=C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	381.21	Volume:	395.748 ? Van der Waals volume.
Dense:	0.963	LogP:	3.478 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.961 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.932 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	77.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.778	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.925	Fsp³:	0.455
MCE-18:	76.188 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.372	Fluc inhibitor:	0.619 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.619 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.449 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.327

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.06	MDCK Permeability:	-4.808
Pgp-inhibitor:	0.99	Pgp-substrate:	0.997
PAMPA:	0.02 ? 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):	0.722
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.898
Plasma Protein Binding (PPB):	92.474%	Volume Distribution (VD):	0.054
Fu:	7.41% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.797
OATP1B3 inhibitor:	0.544	BCRP inhibitor:	0.996
BSEP inhibitor:	0.851

ADMET: Metabolism

CYP1A2-inhibitor:	0.38	CYP1A2-substrate:	0.711
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.061
CYP2C9-inhibitor:	0.181	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.115	CYP2D6-substrate:	0.272
CYP3A4-inhibitor:	0.845	CYP3A4-substrate:	0.169
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.062
HLM stability:	0.922 ? 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):

8.083

Half-life (T1/2):

1.208

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.112
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.216	Rat Oral Acute Toxicity:	0.861
Maximum Recommended Daily Dose:	0.984	Skin Sensitization:	0.999
Carcinogencity:	0.341	Eye Corrosion:	0.0
Eye Irritation:	0.08	Respiratory Toxicity:	0.998
Drug-induced Neurotoxicity:	0.607	Ototoxicity:	0.971
Hematotoxicity:	0.362	Drug-induced Nephrotoxicity:	0.929
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.006
A549 Cytotoxicity:	0.004	Hek293 Cytotoxicity:	0.076
BCF:	1.409 ? 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:	4.217 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.618 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.183 ? 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
NPO64868	Astragalus membranaceus + Penicillium sp. symbiont	Species	n.a.	n.a.	n.a.	n.a.	n.a.	DOI[10.1007/s10600-018-2594-6]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17616609]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17929896]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19113967]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19159274]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19256529]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu	2003	PMID[20303767]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21667925]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21954885]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22106303]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	stem bark of Melia azedarach	n.a.	n.a.	PMID[22409377]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23557488]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23563483]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7622436]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	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
IC50	5
Ki	1
FC	2
Activity	40
Kd	1
Cell survival	4
Inhibition	6
GI50	17

Activity Type	# Activity
Individual protein	5
Cell line	28
Single protein	2
Unchecked	2
Organism	33
Non-molecular	5
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1794	Individual protein	LXR-alpha	Homo sapiens	FC	=	2.05	n.a.	PMID[38334086]
NPT1794	Individual protein	LXR-alpha	Homo sapiens	FC	=	5.01	n.a.	PMID[38334086]
NPT1794	Individual protein	LXR-alpha	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[38334086]
NPT1794	Individual protein	LXR-alpha	Homo sapiens	Kd	=	10.2	nM	PMID[38334086]
NPT21727	Single protein	CDGSH iron-sulfur domain-containing protein 1	Homo sapiens	IC50	=	3387.0	nM	PMID[27687671]
NPT21727	Single protein	CDGSH iron-sulfur domain-containing protein 1	Homo sapiens	Ki	=	145.0	nM	PMID[27687671]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	Cell survival	>	100.0	%	PMID[11931609]
NPT83	Cell line	MCF7	Homo sapiens	Cell survival	=	95.0	%	PMID[11931609]
NPT306	Cell line	PC-3	Homo sapiens	Cell survival	=	99.2	%	PMID[11931609]
NPT306	Cell line	PC-3	Homo sapiens	Cell survival	=	95.6	%	PMID[11931609]
NPT83	Cell line	MCF7	Homo sapiens	Inhibition	>	100.0	%	DrugMatrix in vitro pharmacology data
NPT83	Cell line	MCF7	Homo sapiens	Inhibition	=	95.0	%	PMID[7143358]
NPT306	Cell line	PC-3	Homo sapiens	Inhibition	=	99.2	%	PMID[11754602]
NPT306	Cell line	PC-3	Homo sapiens	Inhibition	=	95.6	%	DOI[10.6019/CHEMBL1201861]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	>	100000.0	nM	PMID[17548494]
NPT111	Cell line	K562	Homo sapiens	GI50	=	2730.0	nM	PMID[17844994]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	=	37100.0	nM	PMID[2292684]
NPT385	Cell line	SR	Homo sapiens	GI50	=	5680.0	nM	PMID[26090896]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	=	21200.0	nM	DrugMatrix in vivo data: Biochemistry
NPT394	Cell line	EKVX	Homo sapiens	GI50	>	100000.0	nM	DrugMatrix in vivo data: Biochemistry
NPT407	Cell line	COLO 205	Homo sapiens	GI50	>	100000.0	nM	PMID[19349520]
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	>	100000.0	nM	PMID[19738026]
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	>	100000.0	nM	PMID[11858756]
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	=	90500.0	nM	PMID[17350734]
NPT306	Cell line	PC-3	Homo sapiens	GI50	=	94000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT90	Cell line	DU-145	Homo sapiens	GI50	>	100000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT457	Cell line	BT-549	Homo sapiens	GI50	=	79700.0	nM	PMID[23046382]
NPT83	Cell line	MCF7	Homo sapiens	GI50	>	100000.0	nM	PMID[25725376]
NPT371	Cell line	UO-31	Homo sapiens	GI50	>	100000.0	nM	PMID[9514009]
NPT111	Cell line	K562	Homo sapiens	IC50	=	41000.0	nM	DrugMatrix in vitro pharmacology data
NPT65	Cell line	HepG2	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[38334086]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	50000.0	nM	PMID[38334086]
NPT28438	Unchecked	Unchecked	n.a.	Activity	n.a.	n.a.	n.a.	PMID[38334086]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	80.1	%	PMID[18321710]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Inhibition	=	79.4	%	PMID[18321710]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	=	11300.0	nM	PMID[18321710]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	GI50	>	100000.0	nM	PMID[18321710]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	68000.0	nM	PMID[18321710]
NPT2	Others	Unspecified	n.a.	IC50	=	250000.0	nM	PMID[19419803]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[38334086]

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
-	Artemia salina	LC50	=	44.8	ug.mL-1	PMID[18330977]

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 NPC303658 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	13886
0.1-0.2	34098
0.2-0.3	1723
0.3-0.4	134
0.4-0.5	14
0.5-0.6	1
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7867	Intermediate Similarity	NPC194740
0.7671	Intermediate Similarity	NPC91179
0.525	Remote Similarity	NPC17059

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC303658 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2615
0.1-0.2	6228
0.2-0.3	295
0.3-0.4	12
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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