NPASS Compound

Natural Product: NPC473838

Natural Product ID	NPC473838
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	VDECHLXUERWMCP-LFWQBVMASA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL453165
PubChem CID	44559857
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0003494] Rhamnofolane and daphnane diterpenoids

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 104110 0 0 0 0 0 0 0 0999 V2000 0.6426 -2.4140 2.0973 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3719 -1.8941 0.8378 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7394 -2.4016 0.8643 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6997 -2.3482 -0.2288 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1266 -2.6832 0.2594 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7030 -1.6860 1.1786 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2386 -0.4341 0.5618 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4303 0.1741 -0.5321 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0655 1.5135 -0.8991 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6061 2.5347 0.1297 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1442 2.7818 -0.1704 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5440 3.8422 0.7311 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1707 4.2016 0.3517 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0734 3.2490 0.4626 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3745 2.8438 -0.6010 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7700 1.8935 -0.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3931 2.0413 -1.8146 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6290 1.4521 -1.5408 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3249 -0.0661 -1.4105 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5175 -0.8302 -1.7657 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7987 -2.1556 -1.5780 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5554 -1.1982 -0.9586 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0005 -2.9963 -0.6251 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5664 -2.6908 -0.9565 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9080 -1.6413 -0.1236 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5509 -1.8569 -0.3827 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6535 -3.2855 -0.9787 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6895 -3.8652 -0.7123 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9017 -4.9977 -0.3900 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8606 -3.2854 -2.4631 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5083 -0.2821 -0.2242 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4521 0.6454 -0.2312 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3187 0.0642 1.0376 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3812 1.1148 0.8053 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9278 2.1060 -0.2436 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7122 2.5528 0.2610 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9078 3.1813 -0.3825 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6983 3.3935 -1.4190 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1208 4.1921 0.7437 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5642 1.8727 2.0183 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7853 1.9463 2.6782 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7656 1.3258 2.1940 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9791 2.7186 3.9175 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4411 0.6535 2.1307 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5055 -2.4721 -2.3141 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1538 -4.3824 -0.8861 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5983 -2.9665 -2.5778 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6447 -3.5814 -1.8830 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0219 -3.2912 1.8827 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4346 -2.6639 2.8761 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0407 -1.6507 2.5723 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4826 -0.7832 1.1237 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2931 -2.0197 1.7911 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6529 -3.5153 1.1520 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5271 -3.2566 -0.8904 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5983 -1.5126 -0.8734 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7360 -2.7065 -0.6671 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1198 -3.7118 0.6685 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1126 -1.4122 2.0707 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6226 -2.1925 1.6388 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2735 -0.6130 0.1411 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3894 0.3163 1.3806 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4117 0.3852 -0.2203 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5164 -0.4197 -1.4914 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1649 1.3849 -0.8380 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7619 1.7846 -1.9139 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7855 2.2104 1.1489 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1930 3.4579 -0.0958 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5021 1.9189 -0.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1260 3.1321 -1.2464 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6446 3.4591 1.7685 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1744 4.7489 0.6792 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8890 5.1003 1.0062 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2433 4.6070 -0.7217 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7701 2.8267 1.3830 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6956 3.2535 -1.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3180 1.6046 -2.3662 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6213 -0.1874 -2.3107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9467 -0.3671 -2.7273 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2628 -2.8838 0.4383 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0985 -1.9724 0.9449 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9642 -1.1291 -1.1183 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4141 -3.8926 -0.4390 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6965 -2.3171 -2.9627 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3931 -4.1570 -2.9669 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9674 -3.4726 -2.6414 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8222 -0.7942 1.4674 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3747 0.7645 0.5788 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4159 4.2463 -1.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7153 2.7839 -2.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9310 5.1757 0.2111 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1752 4.1695 0.9972 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3801 4.1194 1.5235 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0961 3.8024 3.6877 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8712 2.3654 4.4743 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1138 2.5446 4.6091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5352 0.0235 3.0435 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3867 0.5571 1.7875 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7001 1.6867 2.3675 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7613 -3.2207 -2.8704 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9626 -4.7307 -0.4271 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0466 -2.3186 -3.3592 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0305 -3.7872 -3.0515 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5284 -3.3293 -2.2381 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 3 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 1 0 21 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 27 30 1 0 25 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 35 37 1 0 37 38 2 0 37 39 1 0 34 40 1 0 40 41 1 0 41 42 2 0 41 43 1 0 33 44 1 0 24 45 1 0 23 46 1 0 21 47 1 0 47 48 1 0 26 2 1 0 32 16 1 0 36 16 1 0 35 18 1 0 31 19 1 0 22 20 1 0 28 24 1 0 1 49 1 0 1 50 1 0 1 51 1 0 2 52 1 0 3 53 1 0 3 54 1 0 4 55 1 0 4 56 1 0 5 57 1 0 5 58 1 0 6 59 1 0 6 60 1 0 7 61 1 0 7 62 1 0 8 63 1 0 8 64 1 0 9 65 1 0 9 66 1 0 10 67 1 0 10 68 1 0 11 69 1 0 11 70 1 0 12 71 1 0 12 72 1 0 13 73 1 0 13 74 1 0 14 75 1 0 15 76 1 0 18 77 1 0 19 78 1 0 20 79 1 0 23 80 1 0 25 81 1 0 26 82 1 0 27 83 1 0 30 84 1 0 30 85 1 0 30 86 1 0 33 87 1 0 34 88 1 0 38 89 1 0 38 90 1 0 39 91 1 0 39 92 1 0 39 93 1 0 43 94 1 0 43 95 1 0 43 96 1 0 44 97 1 0 44 98 1 0 44 99 1 0 45100 1 0 46101 1 0 47102 1 0 47103 1 0 48104 1 0 M END

Standard InCHIKey	VDECHLXUERWMCP-LFWQBVMASA-N
Standard InCHI	InChI=1S/C38H56O10/c1-21(2)37-30(44-25(6)40)24(5)38-27-31-34(20-39,45-31)33(42)36(43)28(38)26(23(4)29(36)41)22(3)18-16-14-12-10-8-7-9-11-13-15-17-19-35(47-37,48-38)46-32(27)37/h17,19,22-24,26-28,30-33,39,42-43H,1,7-16,18,20H2,2-6H3/b19-17+/t22-,23-,24+,26-,27-,28+,30+,31-,32+,33+,34-,35+,36+,37+,38+/m0/s1
SMILES	CC1CCCCCCCCCCCC=CC23OC4C5C6C(O6)(C(C7(C(C1C(C7=O)C)C5(O2)C(C(C4(O3)C(=C)C)OC(=O)C)C)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	672.39	Volume:	683.265 ? Van der Waals volume.
Dense:	0.984	LogP:	5.98 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.836 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.511 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	42.0
TPSA:	144.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	7.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.222	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.738	Fsp³:	0.842
MCE-18:	183.4 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.354	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.083 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.057	Promiscuous compounds:	0.017

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.097	MDCK Permeability:	-4.737
Pgp-inhibitor:	0.266	Pgp-substrate:	0.0
PAMPA:	0.001 ? 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%):	0.003	30% Bioavailability (F30%):	0.348
50% Bioavailability (F50%):	0.913

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.433	MRP1:	1.0
Plasma Protein Binding (PPB):	91.655%	Volume Distribution (VD):	-0.002
Fu:	6.119% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.034
OATP1B3 inhibitor:	0.952	BCRP inhibitor:	0.007
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.639	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.017
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.971
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.215
HLM stability:	0.99 ? 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):

2.46

Half-life (T1/2):

1.491

ADMET: Toxicity

hERG Blockers:	0.089	hERG Blockers (10um):	0.452
Human Hepatotoxicity (H-HT):	0.267	Drug-induced Liver Injury (DILI):	0.082
AMES Toxicity:	0.225	Rat Oral Acute Toxicity:	0.398
Maximum Recommended Daily Dose:	0.847	Skin Sensitization:	0.907
Carcinogencity:	0.02	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.234
Drug-induced Neurotoxicity:	0.259	Ototoxicity:	0.942
Hematotoxicity:	0.092	Drug-induced Nephrotoxicity:	0.007
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.434
A549 Cytotoxicity:	0.133	Hek293 Cytotoxicity:	0.888
BCF:	1.913 ? 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:	4.208 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.703 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.051 ? 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
NPO32646	synaptolepis kirkii	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000015]
NPO33116	synaptolepis retusa	Species	Thymelaeaceae	Eukaryota	roots	n.a.	n.a.	PMID[3210015]
NPO32646	synaptolepis kirkii	Species	Thymelaeaceae	Eukaryota	roots	n.a.	n.a.	PMID[3210015]
NPO33116	synaptolepis retusa	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	10
Survival	2

Activity Type	# Activity
Organism	12

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

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	=	0.01	nmol	PMID[24437979]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	100.0	/nmol	PMID[22959244]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	33.0	%	PMID[8946747]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	0.0	%	PMID[20695427]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	100.0	%	PMID[22959244]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	27.0	%	PubChem BioAssay data set
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	0.33	n.a.	PMID[23756062]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	0.0	n.a.	PMID[20695427]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	4.4	n.a.	PMID[20381348]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	0.6	n.a.	PMID[22959244]
NPT32	Organism	Mus musculus	Mus musculus	Survival	=	99.0	%	PMID[22959244]
NPT32	Organism	Mus musculus	Mus musculus	Survival	=	94.0	%	PMID[23756062]

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 NPC473838 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	19258
0.1-0.2	29064
0.2-0.3	1436
0.3-0.4	44
0.4-0.5	30
0.5-0.6	16
0.6-0.7	9
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
0.7407	Intermediate Similarity	NPC476078
0.6786	Remote Similarity	NPC180902
0.625	Remote Similarity	NPC182266
0.625	Remote Similarity	NPC475154
0.625	Remote Similarity	NPC485700
0.6136	Remote Similarity	NPC223356
0.6136	Remote Similarity	NPC298697
0.6136	Remote Similarity	NPC475500
0.6136	Remote Similarity	NPC100017
0.6136	Remote Similarity	NPC481742
0.5957	Remote Similarity	NPC475389
0.5909	Remote Similarity	NPC476091
0.573	Remote Similarity	NPC324104
0.573	Remote Similarity	NPC473548
0.5714	Remote Similarity	NPC75831
0.5714	Remote Similarity	NPC471137
0.5698	Remote Similarity	NPC142882
0.5698	Remote Similarity	NPC608716
0.5698	Remote Similarity	NPC609033
0.5652	Remote Similarity	NPC471136
0.5652	Remote Similarity	NPC116727
0.5652	Remote Similarity	NPC39509
0.5591	Remote Similarity	NPC481744
0.5591	Remote Similarity	NPC481743
0.5347	Remote Similarity	NPC486153
0.5222	Remote Similarity	NPC162495

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473838 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6550
0.1-0.2	2589
0.2-0.3	11
0.3-0.4	0
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