NPASS Compound

Natural Product: NPC92558

Natural Product ID	NPC92558
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Leukotriene A4
IUPAC Name	4-[(2S,3S)-3-[(1E,3E,5Z,8Z)-tetradeca-1,3,5,8-tetraenyl]oxiran-2-yl]butanoic acid
Synonyms	Leukotriene A4
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL69439
PubChem CID	5280383
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000262] Fatty acids and conjugates [CHEMONTID:0001989] Heterocyclic fatty acids [CHEMONTID:0001537] Epoxy fatty 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 53 53 0 0 0 0 0 0 0 0999 V2000 -7.0549 -1.0212 -1.5421 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1162 -0.9869 -0.3431 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5489 0.0489 0.6594 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5807 1.4441 0.1473 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1952 1.9165 -0.2387 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3769 1.9077 0.9700 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2653 1.2795 1.1709 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6537 0.4400 0.1144 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5667 -0.9149 0.6599 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4521 -1.5808 0.7986 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1921 -1.0206 0.4156 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8928 -1.7499 0.5855 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1882 -1.2132 0.2079 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3074 -1.9168 0.3630 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6012 -1.3125 -0.0423 C 0 0 2 0 0 0 0 0 0 0 0 0 5.4476 -0.8736 0.9473 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7494 0.1522 0.3703 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2972 1.0503 -0.6726 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6686 0.7074 -1.1756 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7346 0.7130 -0.1348 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0222 0.3511 -0.8226 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0851 0.1066 -2.0520 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1619 0.2927 -0.0503 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6658 -0.3585 -2.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0609 -0.7517 -1.2040 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0452 -2.0495 -1.9333 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2318 -1.9805 0.1688 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1063 -0.9145 -0.7116 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5533 -0.2666 1.0220 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8249 -0.0577 1.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0268 2.0957 0.9356 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2558 1.4569 -0.7444 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8884 1.3057 -1.0769 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3490 2.9988 -0.5473 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7851 2.5282 1.8080 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7528 1.3516 2.1184 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6135 0.8524 -0.0746 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2037 0.3831 -0.8275 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5147 -1.3818 0.9716 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4974 -2.6205 1.2315 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0686 -0.0624 0.0027 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8175 -2.7597 1.0110 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2415 -0.2208 -0.2079 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2222 -2.9102 0.7830 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9925 -1.5944 -1.0355 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9597 0.5928 1.0130 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2114 2.1105 -0.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6153 0.9704 -1.5710 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6970 -0.2244 -1.7557 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9366 1.5218 -1.9114 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9117 1.7288 0.2896 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6083 -0.0503 0.6586 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0768 0.4871 -0.4794 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 17 15 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 0 2 28 1 0 3 29 1 0 3 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 7 36 1 0 8 37 1 0 8 38 1 0 9 39 1 0 10 40 1 0 11 41 1 0 12 42 1 0 13 43 1 0 14 44 1 0 15 45 1 6 17 46 1 1 18 47 1 0 18 48 1 0 19 49 1 0 19 50 1 0 20 51 1 0 20 52 1 0 23 53 1 0 M END

Standard InCHIKey	UFPQIRYSPUYQHK-WAQVJNLQSA-N
Standard InCHI	InChI=1S/C20H30O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-15-18-19(23-18)16-14-17-20(21)22/h6-7,9-13,15,18-19H,2-5,8,14,16-17H2,1H3,(H,21,22)/b7-6-,10-9-,12-11+,15-13+/t18-,19-/m0/s1
SMILES	CCCCC/C=CC/C=CC=CC=C[C@@H]1O[C@H]1CCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.22	Volume:	359.108 ? Van der Waals volume.
Dense:	0.886	LogP:	4.642 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.252 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.608 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	8.0
TPSA:	49.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.22	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.789	Fsp³:	0.55
MCE-18:	12.774 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.209	Fluc inhibitor:	0.419 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.017 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.029 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.872	Promiscuous compounds:	0.196

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.173	MDCK Permeability:	-4.958
Pgp-inhibitor:	0.004	Pgp-substrate:	0.007
PAMPA:	0.208 ? 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):	0.005
20% Bioavailability (F20%):	0.051	30% Bioavailability (F30%):	0.217
50% Bioavailability (F50%):	0.412

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.998
Plasma Protein Binding (PPB):	97.818%	Volume Distribution (VD):	-0.603
Fu:	1.799% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.089
OATP1B3 inhibitor:	0.823	BCRP inhibitor:	0.034
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.338
CYP2C19-inhibitor:	0.037	CYP2C19-substrate:	0.1
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.04
CYP2D6-inhibitor:	0.248	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.027 ? 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):

6.806

Half-life (T1/2):

0.623

ADMET: Toxicity

hERG Blockers:	0.212	hERG Blockers (10um):	0.326
Human Hepatotoxicity (H-HT):	0.223	Drug-induced Liver Injury (DILI):	0.004
AMES Toxicity:	0.418	Rat Oral Acute Toxicity:	0.077
Maximum Recommended Daily Dose:	0.257	Skin Sensitization:	1.0
Carcinogencity:	0.113	Eye Corrosion:	0.777
Eye Irritation:	0.985	Respiratory Toxicity:	0.88
Drug-induced Neurotoxicity:	0.015	Ototoxicity:	0.53
Hematotoxicity:	0.031	Drug-induced Nephrotoxicity:	0.251
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.079	Hek293 Cytotoxicity:	0.1
BCF:	1.056 ? 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:	3.909 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.216 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.008 ? 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
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1172/JCI16309]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1371/journal.pone.0115359]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[10557354]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11034610]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11419736]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11530998]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1175644]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12391014]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12812989]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12840027]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12878451]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15084647]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1521032]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15230696]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15314235]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[16112079]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[16770722]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1687010]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17116739]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17190852]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17875433]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18311922]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18544912]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18799520]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[19425150]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[19961175]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20506249]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20601097]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	bile	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	faeces	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	urine	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20876113]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[21798258]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[2268561]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[22711758]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23315938]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23717534]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23752203]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23810710]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23811455]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23868375]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23919613]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24101735]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24399466]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24494566]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24558969]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24816727]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25114169]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25181601]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25293588]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25644343]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[26236990]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[27471436]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[3179836]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[347637]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[4696527]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[5432584]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[6121420]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[6780563]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[8600370]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[8987136]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[9192820]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[9800648]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	Database[MetaboLights]
NPO20338	Mus musculus	Species	Muridae	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
Inhibition	1
IC50	1
Ratio	1

Activity Type	# Activity
Individual protein	2
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	78.0	%	PMID[6298421]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	IC50	=	2000.0	nM	PMID[6298421]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Ratio	=	0.0009	n.a.	PMID[8423594]

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 NPC92558 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	31139
0.1-0.2	17443
0.2-0.3	1052
0.3-0.4	126
0.4-0.5	50
0.5-0.6	35
0.6-0.7	10
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
0.6735	Remote Similarity	NPC320642
0.6531	Remote Similarity	NPC317583
0.6136	Remote Similarity	NPC321062
0.6	Remote Similarity	NPC323597
0.6	Remote Similarity	NPC211752
0.6	Remote Similarity	NPC323498
0.6	Remote Similarity	NPC154245
0.6	Remote Similarity	NPC85813
0.6	Remote Similarity	NPC223697
0.6	Remote Similarity	NPC6095
0.5926	Remote Similarity	NPC329249
0.5778	Remote Similarity	NPC91495
0.5778	Remote Similarity	NPC5413
0.5769	Remote Similarity	NPC329550
0.566	Remote Similarity	NPC328311
0.5652	Remote Similarity	NPC59051
0.5435	Remote Similarity	NPC70387
0.5397	Remote Similarity	NPC319021
0.537	Remote Similarity	NPC323045
0.537	Remote Similarity	NPC317881
0.5333	Remote Similarity	NPC424
0.5333	Remote Similarity	NPC36061
0.5333	Remote Similarity	NPC69510
0.5333	Remote Similarity	NPC77272
0.5333	Remote Similarity	NPC290563
0.5333	Remote Similarity	NPC139029
0.5333	Remote Similarity	NPC281972
0.5333	Remote Similarity	NPC261831
0.5333	Remote Similarity	NPC87564
0.5319	Remote Similarity	NPC52955
0.5319	Remote Similarity	NPC88966
0.5319	Remote Similarity	NPC25417
0.5319	Remote Similarity	NPC1813
0.5283	Remote Similarity	NPC320305
0.5283	Remote Similarity	NPC68343
0.5283	Remote Similarity	NPC328089
0.5273	Remote Similarity	NPC322461
0.5217	Remote Similarity	NPC95145
0.5217	Remote Similarity	NPC325642
0.5217	Remote Similarity	NPC65174
0.5185	Remote Similarity	NPC325977
0.5179	Remote Similarity	NPC605544
0.5179	Remote Similarity	NPC607260
0.5111	Remote Similarity	NPC281245
0.5075	Remote Similarity	NPC319473

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC92558 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6308
0.1-0.2	2688
0.2-0.3	123
0.3-0.4	17
0.4-0.5	8
0.5-0.6	4
0.6-0.7	1
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
0.6	Remote Similarity	NPD4266	Phase 2
0.5778	Remote Similarity	NPD3173	Phase 4
0.5333	Remote Similarity	NPD3195	Phase 2
0.5333	Remote Similarity	NPD3196	Approved
0.5319	Remote Similarity	NPD3172	Approved

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