NPASS Compound

Natural Product: NPC110094

Natural Product ID	NPC110094
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	20-Epikoetjapic Acid
IUPAC Name	(3R,4aR,6aR,7S,8S,10aR,10bS,12aS)-7-(2-carboxyethyl)-3,7,10a,10b,12a-pentamethyl-8-prop-1-en-2-yl-2,4,4a,6,6a,8,9,10,11,12-decahydro-1H-chrysene-3-carboxylic acid
Synonyms	20-Epikoetjapic Acid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL517189
PubChem CID	10790564
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003364] Steroid acids

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 80 83 0 0 0 0 0 0 0 0999 V2000 -6.1247 -1.3726 -0.2206 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8243 -1.5537 0.0252 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4576 -2.7530 0.8444 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8159 -0.6232 -0.5628 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0080 -1.4672 -1.5154 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6170 -1.0276 -1.7598 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8877 -0.8195 -0.4575 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7269 -2.1715 0.1920 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6024 0.1622 0.4268 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9523 0.1169 1.7870 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5152 0.0725 1.6468 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2069 -0.1067 0.5392 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6757 -0.1104 0.6625 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2289 1.2918 0.4985 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6908 1.3443 0.8848 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8010 1.8499 2.3073 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3192 -0.0281 0.8273 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8169 -0.8080 -0.3688 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3230 -1.1057 -0.2289 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2069 -2.4680 0.3925 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7339 -1.0295 -1.5969 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2598 -1.2153 -1.6824 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4897 -0.2862 -0.7720 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5026 1.0598 -1.4250 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4209 2.3195 0.0220 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7812 2.9535 -0.8785 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7593 2.5454 0.1786 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0662 0.1480 0.4419 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.6412 -0.2159 1.8340 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5443 1.6226 0.3320 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3298 2.2510 -0.9772 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8509 3.6665 -0.9416 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3581 4.0856 0.1203 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7855 4.5060 -2.0358 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4278 -0.5269 -0.8027 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8560 -2.0602 0.1568 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3980 -2.9753 0.8805 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9113 -3.6830 0.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8798 -2.7066 1.8411 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4384 0.0454 -1.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5449 -1.5192 -2.4828 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9928 -2.5303 -1.1538 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6125 -0.1963 -2.4518 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0929 -1.8810 -2.2753 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3374 -2.4521 0.3292 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1588 -2.2368 1.2092 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1413 -2.9979 -0.4557 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2641 1.1750 0.0348 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2788 -0.6569 2.4609 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1908 1.1023 2.2856 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0579 0.2097 2.6052 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9559 -0.3911 1.7232 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6098 1.9468 1.1638 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1509 1.6964 -0.5091 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7769 1.5692 2.7465 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9308 1.4965 2.8796 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7230 2.9745 2.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1618 -0.5458 1.7791 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4094 0.1052 0.6833 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4171 -1.7387 -0.4301 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0229 -0.2225 -1.2777 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5267 -2.4331 1.2938 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1851 -2.7702 0.8032 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8354 -3.2443 -0.3060 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1948 -1.8772 -2.1853 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0423 -0.0674 -2.0470 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0118 -2.2686 -1.5816 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9626 -0.9263 -2.7340 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4279 1.1639 -2.0689 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5715 1.8945 -0.6771 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3191 1.2925 -2.0931 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3373 2.7838 -0.6378 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5962 0.6688 2.5155 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2144 -1.1082 2.2575 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7216 -0.3673 1.6616 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0947 2.2067 1.1600 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6448 1.5873 0.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2241 2.3756 -1.1810 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7283 1.7729 -1.8653 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0570 5.4826 -1.9048 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 1 7 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 1 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 1 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 6 15 25 1 0 25 26 2 0 25 27 1 0 9 28 1 0 28 29 1 1 28 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 32 34 1 0 28 4 1 0 23 7 1 0 23 12 1 0 19 13 1 0 1 35 1 0 1 36 1 0 3 37 1 0 3 38 1 0 3 39 1 0 4 40 1 6 5 41 1 0 5 42 1 0 6 43 1 0 6 44 1 0 8 45 1 0 8 46 1 0 8 47 1 0 9 48 1 6 10 49 1 0 10 50 1 0 11 51 1 0 13 52 1 1 14 53 1 0 14 54 1 0 16 55 1 0 16 56 1 0 16 57 1 0 17 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 20 62 1 0 20 63 1 0 20 64 1 0 21 65 1 0 21 66 1 0 22 67 1 0 22 68 1 0 24 69 1 0 24 70 1 0 24 71 1 0 27 72 1 0 29 73 1 0 29 74 1 0 29 75 1 0 30 76 1 0 30 77 1 0 31 78 1 0 31 79 1 0 34 80 1 0 M END

Standard InCHIKey	ASOUKQDZWGOCBR-TYAUOZCYSA-N
Standard InCHI	InChI=1S/C30H46O4/c1-19(2)20-10-13-30(7)23(28(20,5)12-11-24(31)32)9-8-21-22-18-27(4,25(33)34)15-14-26(22,3)16-17-29(21,30)6/h8,20,22-23H,1,9-18H2,2-7H3,(H,31,32)(H,33,34)/t20-,22-,23+,26+,27+,28-,29+,30+/m0/s1
SMILES	C=C(C)[C@@H]1CC[C@]2(C)[C@H](CC=C3[C@@H]4C[C@@](C)(CC[C@]4(C)CC[C@@]23C)C(=O)O)[C@@]1(C)CCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.34	Volume:	517.825 ? Van der Waals volume.
Dense:	0.908	LogP:	3.842 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.088 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.184 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	74.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.408	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.804	Fsp³:	0.8
MCE-18:	88.148 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.773	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.031 ? 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:	0.645	Promiscuous compounds:	0.08

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.134	MDCK Permeability:	-4.963
Pgp-inhibitor:	0.023	Pgp-substrate:	0.0
PAMPA:	0.978 ? 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):	0.0
20% Bioavailability (F20%):	0.023	30% Bioavailability (F30%):	0.004
50% Bioavailability (F50%):	0.116

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.13	MRP1:	0.999
Plasma Protein Binding (PPB):	97.385%	Volume Distribution (VD):	-0.523
Fu:	3.127% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.024	BCRP inhibitor:	0.001
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.816	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.181	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.002
HLM stability:	0.0 ? 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):

1.127

Half-life (T1/2):

1.32

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.049
Human Hepatotoxicity (H-HT):	0.574	Drug-induced Liver Injury (DILI):	0.362
AMES Toxicity:	0.043	Rat Oral Acute Toxicity:	0.461
Maximum Recommended Daily Dose:	0.689	Skin Sensitization:	0.742
Carcinogencity:	0.631	Eye Corrosion:	0.008
Eye Irritation:	0.465	Respiratory Toxicity:	0.948
Drug-induced Neurotoxicity:	0.155	Ototoxicity:	0.767
Hematotoxicity:	0.47	Drug-induced Nephrotoxicity:	0.703
Genotoxicity:	0.758	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.017	Hek293 Cytotoxicity:	0.06
BCF:	0.739 ? 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:	3.661 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.075 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.22 ? 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
NPO13817	Maytenus undata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10843569]
NPO26165	Sandoricum indicum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11575968]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[19743809]
NPO631	Osyris lanceolata	Species	Santalaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20499922]
NPO4016	Ligularia fischeri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24892518]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	n.a.	n.a.	PMID[25924111]
NPO13817	Maytenus undata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26165	Sandoricum indicum	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2871	Canistrocarpus cervicornis	Species	Dictyotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4016	Ligularia fischeri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4016	Ligularia fischeri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4016	Ligularia fischeri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8412	Monanchora arbuscula	Species	Crambeidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13817	Maytenus undata	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2871	Canistrocarpus cervicornis	Species	Dictyotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8117	Aureolaria virginica	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4016	Ligularia fischeri	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO631	Osyris lanceolata	Species	Santalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26165	Sandoricum indicum	Species	Meliaceae	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
MIC	9
IC50	8

Activity Type	# Activity
Cell line	5
Organism	8
Others	2
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2831	Cell line	P388/S	Mus musculus	IC50	>	25.0	ug.mL-1	PMID[11575968]
NPT168	Cell line	P388	Mus musculus	IC50	>	25.0	ug.mL-1	PMID[11575968]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1900.0	nM	PMID[10843569]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	500.0	nM	PMID[10843569]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	0.01	ug	PMID[20499922]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	0.001	ug	PMID[20499922]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	3.25	ug.mL-1	PMID[10843569]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	6.25	ug.mL-1	PMID[10843569]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	6.25	ug.mL-1	PMID[10843569]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	0.001	ug	PMID[20499922]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	0.01	ug	PMID[20499922]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	=	0.01	ug	PMID[20499922]
NPT1	Others	Radical scavenging activity	n.a.	MIC	=	10.0	ug	PMID[20499922]
NPT2	Others	Unspecified	n.a.	IC50	>	100.0	ug.mL-1	PMID[11575968]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC110094 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	31189
0.1-0.2	16073
0.2-0.3	2050
0.3-0.4	432
0.4-0.5	80
0.5-0.6	7
0.6-0.7	16
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	Natural Product ID
1.0	High Similarity	NPC260385
0.7385	Intermediate Similarity	NPC104545
0.7097	Intermediate Similarity	NPC107039
0.6567	Remote Similarity	NPC263272
0.6567	Remote Similarity	NPC171203
0.6567	Remote Similarity	NPC307426
0.6567	Remote Similarity	NPC98442
0.6567	Remote Similarity	NPC242468
0.6429	Remote Similarity	NPC78580
0.6377	Remote Similarity	NPC155120
0.6377	Remote Similarity	NPC288833
0.6286	Remote Similarity	NPC263393
0.6286	Remote Similarity	NPC474964
0.6286	Remote Similarity	NPC474525
0.6197	Remote Similarity	NPC46441
0.6197	Remote Similarity	NPC476064
0.6154	Remote Similarity	NPC471899
0.6094	Remote Similarity	NPC221647
0.6	Remote Similarity	NPC474537
0.5882	Remote Similarity	NPC231431
0.5753	Remote Similarity	NPC474529
0.5672	Remote Similarity	NPC471897
0.5652	Remote Similarity	NPC199595
0.5301	Remote Similarity	NPC473938
0.5211	Remote Similarity	NPC280654
0.5122	Remote Similarity	NPC476878

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC110094 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7167
0.1-0.2	1928
0.2-0.3	46
0.3-0.4	6
0.4-0.5	3
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