NPASS Compound

Natural Product: NPC473669

Natural Product ID	NPC473669
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-2-Methyl-4-[(2R,13S)-2,5,13-Trihydroxy-13-[(2S,5S)-5-[(1S)-1-Hydroxytridecyl]Oxolan-2-Yl]Tridecyl]-2H-Furan-5-One
IUPAC Name	(2S)-2-methyl-4-[(2R,13S)-2,5,13-trihydroxy-13-[(2S,5S)-5-[(1S)-1-hydroxytridecyl]oxolan-2-yl]tridecyl]-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448646
PubChem CID	10817327
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 106107 0 0 0 0 0 0 0 0999 V2000 11.2123 -3.9152 4.3074 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2478 -2.5660 3.6289 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8683 -2.1311 3.1849 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8926 -0.7713 2.5299 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7838 -0.7702 1.3168 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8608 0.5533 0.6419 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5848 1.1156 0.1148 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9328 0.2702 -0.9218 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6887 0.9019 -1.4712 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6653 1.0986 -0.4151 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4068 1.7948 -0.9555 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7900 0.9902 -2.0431 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5727 1.6308 -2.6460 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5089 1.8147 -1.5614 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9661 0.4753 -1.1309 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5019 0.8037 -0.8489 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2607 1.8767 -1.8566 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4494 2.5085 -2.0848 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8719 2.7979 -1.5704 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2195 2.0967 -1.3913 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6156 1.3283 -2.5873 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9222 0.6329 -2.5127 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1802 1.3673 -2.4109 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4625 2.2696 -1.2714 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3928 1.6326 0.0919 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4272 0.5115 0.1242 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4337 -0.1740 1.4651 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4730 -1.2628 1.4697 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1949 -2.2716 0.4424 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0711 -3.4480 0.3236 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.4906 -3.3145 0.0174 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3357 -2.5314 0.9513 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0531 -1.4534 0.6709 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7323 -1.0094 1.8952 C 0 0 1 0 0 0 0 0 0 0 0 0 -11.3613 -1.8786 2.9214 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.5127 -2.8204 2.3560 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9932 -3.7818 3.0301 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2811 0.4107 2.1847 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9395 -4.2050 1.5181 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7377 0.8014 2.4388 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0573 3.6599 -2.6546 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9778 2.8879 -3.1237 O 0 0 0 0 0 0 0 0 0 0 0 0 10.8060 -4.7039 3.6454 H 0 0 0 0 0 0 0 0 0 0 0 0 12.2630 -4.2252 4.5192 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7114 -3.8770 5.3037 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6509 -1.8348 4.3372 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9235 -2.7091 2.7396 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1887 -2.1276 4.0472 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4775 -2.9089 2.4845 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8386 -0.5340 2.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2495 -0.0554 3.2999 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8263 -0.9754 1.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5531 -1.6240 0.6654 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6316 0.4698 -0.1592 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2633 1.2799 1.4055 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9453 1.3861 0.9829 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8420 2.0896 -0.3712 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6382 -0.7360 -0.5533 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6618 0.1950 -1.7747 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9432 1.8431 -2.0151 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2988 0.2205 -2.2924 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2792 0.1152 -0.0104 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0888 1.6869 0.4158 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7340 1.8404 -0.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6960 2.8032 -1.2779 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5612 -0.0407 -1.6438 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5256 0.7970 -2.8657 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2279 1.0478 -3.4943 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8982 2.3486 -0.6880 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4651 0.0438 -0.2649 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9424 -0.2457 -2.0040 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1426 -0.0900 -0.9971 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4449 1.1652 0.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0125 1.3402 -2.8261 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7185 3.3740 -0.6481 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1536 1.4461 -0.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9245 2.9081 -1.1832 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5815 2.0229 -3.4774 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8041 0.5386 -2.7902 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9102 -0.1129 -1.6298 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9824 -0.0808 -3.4207 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0819 0.6826 -2.5073 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2825 2.0147 -3.3438 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6160 2.4810 -1.3801 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0519 3.2821 -1.3172 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6880 2.4211 0.8262 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3952 1.2799 0.3377 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4119 0.9062 -0.1179 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0852 -0.2031 -0.6592 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4303 -0.5641 1.7493 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4992 -1.6814 2.5145 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4424 -0.7297 1.3600 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2088 -1.7764 -0.5847 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1166 -2.5863 0.5445 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6399 -4.1744 -0.4528 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7129 -3.0374 -1.0501 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9291 -4.3660 0.0700 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1127 -0.9899 -0.3126 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8430 -1.0611 1.8088 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0675 0.5234 3.2633 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3542 0.6612 1.6276 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0756 1.1256 1.8860 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0384 -4.0444 1.9241 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4655 1.3524 2.0686 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7245 3.3159 -3.4979 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4899 3.1611 -3.9416 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 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 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 2 0 34 38 1 0 30 39 1 0 27 40 1 0 19 41 1 0 13 42 1 0 18 14 1 0 36 32 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 0 2 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 5 52 1 0 5 53 1 0 6 54 1 0 6 55 1 0 7 56 1 0 7 57 1 0 8 58 1 0 8 59 1 0 9 60 1 0 9 61 1 0 10 62 1 0 10 63 1 0 11 64 1 0 11 65 1 0 12 66 1 0 12 67 1 0 13 68 1 6 14 69 1 1 15 70 1 0 15 71 1 0 16 72 1 0 16 73 1 0 17 74 1 6 19 75 1 1 20 76 1 0 20 77 1 0 21 78 1 0 21 79 1 0 22 80 1 0 22 81 1 0 23 82 1 0 23 83 1 0 24 84 1 0 24 85 1 0 25 86 1 0 25 87 1 0 26 88 1 0 26 89 1 0 27 90 1 0 28 91 1 0 28 92 1 0 29 93 1 0 29 94 1 0 30 95 1 6 31 96 1 0 31 97 1 0 33 98 1 0 34 99 1 6 38100 1 0 38101 1 0 38102 1 0 39103 1 0 40104 1 0 41105 1 0 42106 1 0 M END

Standard InCHIKey	SZFHVTSTVQGVKY-BDEAOZRMSA-N
Standard InCHI	InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-13-16-19-31(38)33-23-24-34(42-33)32(39)20-17-14-11-12-15-18-29(36)21-22-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29?,30+,31-,32-,33-,34-/m0/s1
SMILES	CCCCCCCCCCCC[C@@H]([C@@H]1CC[C@H](O1)[C@H](CCCCCCCC(CC[C@H](CC1=C[C@@H](OC1=O)C)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	596.47	Volume:	653.062 ? Van der Waals volume.
Dense:	0.913	LogP:	5.229 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.536 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.382 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	11.0
TPSA:	116.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.062	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.617	Fsp³:	0.914
MCE-18:	32.239 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.802	Fluc inhibitor:	0.012 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.082 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.542	Promiscuous compounds:	0.145

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.196	MDCK Permeability:	-4.866
Pgp-inhibitor:	0.0	Pgp-substrate:	0.981
PAMPA:	0.79 ? 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%):	0.991	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.9
Plasma Protein Binding (PPB):	97.407%	Volume Distribution (VD):	0.884
Fu:	3.033% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.826
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.628
BSEP inhibitor:	0.725

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.918	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.014	CYP2D6-substrate:	0.398
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.979
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.962
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):

6.194

Half-life (T1/2):

1.086

ADMET: Toxicity

hERG Blockers:	0.488	hERG Blockers (10um):	0.801
Human Hepatotoxicity (H-HT):	0.656	Drug-induced Liver Injury (DILI):	0.154
AMES Toxicity:	0.169	Rat Oral Acute Toxicity:	0.028
Maximum Recommended Daily Dose:	0.901	Skin Sensitization:	1.0
Carcinogencity:	0.393	Eye Corrosion:	0.006
Eye Irritation:	0.666	Respiratory Toxicity:	0.949
Drug-induced Neurotoxicity:	0.054	Ototoxicity:	0.895
Hematotoxicity:	0.101	Drug-induced Nephrotoxicity:	0.948
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.082
A549 Cytotoxicity:	0.945	Hek293 Cytotoxicity:	0.23
BCF:	1.203 ? 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:	4.965 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.174 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.877 ? 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
NPO32906	annona cherimilia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10514307]

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
ED50	6
Selectivity ratio	1

Activity Type	# Activity
Cell line	7

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
NPT81	Cell line	A549	Homo sapiens	ED50	=	1.63	ug ml-1	PMID[25237727]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.011	ug ml-1	PMID[25237727]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	0.001	ug ml-1	PMID[23964704]
NPT376	Cell line	A498	Homo sapiens	ED50	=	2.96	ug ml-1	PMID[16562846]
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	1.32	ug ml-1	PMID[24928403]
NPT783	Cell line	MIA PaCa-2	Homo sapiens	ED50	=	0.001	ug ml-1	PMID[18824363]
NPT376	Cell line	A498	Homo sapiens	Selectivity ratio	=	1000.0	n.a.	PMID[10514307]

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
-	Artemia salina	LC50	=	0.0125	ug.mL-1	PMID[25237727]

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 NPC473669 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	15951
0.1-0.2	30283
0.2-0.3	3260
0.3-0.4	124
0.4-0.5	29
0.5-0.6	14
0.6-0.7	45
0.7-0.8	0
0.8-0.85	37
0.85-0.9	16
0.9-0.95	0
0.95-1	22

Similarity Score	Similarity Level	Natural Product ID
0.9762	High Similarity	NPC232555
0.9762	High Similarity	NPC171174
0.9762	High Similarity	NPC114694
0.9762	High Similarity	NPC485248
0.9762	High Similarity	NPC142117
0.9762	High Similarity	NPC480249
0.9762	High Similarity	NPC485249
0.9762	High Similarity	NPC240695
0.9756	High Similarity	NPC107986
0.9756	High Similarity	NPC223871
0.9756	High Similarity	NPC231009
0.9756	High Similarity	NPC103284
0.9756	High Similarity	NPC110710
0.9756	High Similarity	NPC1083
0.9756	High Similarity	NPC82795
0.9756	High Similarity	NPC286338
0.9756	High Similarity	NPC603931
0.9756	High Similarity	NPC604237
0.9535	High Similarity	NPC488632
0.9524	High Similarity	NPC488253
0.9524	High Similarity	NPC488251
0.9512	High Similarity	NPC606043
0.8889	High Similarity	NPC280621
0.8889	High Similarity	NPC48338
0.8889	High Similarity	NPC488628
0.8864	High Similarity	NPC182383
0.8696	High Similarity	NPC178215
0.8696	High Similarity	NPC42598
0.8667	High Similarity	NPC93794
0.8667	High Similarity	NPC134865
0.8667	High Similarity	NPC473504
0.8667	High Similarity	NPC103523
0.8667	High Similarity	NPC81778
0.8667	High Similarity	NPC40066
0.8667	High Similarity	NPC488627
0.8667	High Similarity	NPC47937
0.8667	High Similarity	NPC488631
0.8511	High Similarity	NPC488250
0.8444	Intermediate Similarity	NPC81045
0.8444	Intermediate Similarity	NPC39754
0.8444	Intermediate Similarity	NPC171135
0.8444	Intermediate Similarity	NPC61257
0.8444	Intermediate Similarity	NPC320569
0.8444	Intermediate Similarity	NPC133730
0.8444	Intermediate Similarity	NPC191929
0.8444	Intermediate Similarity	NPC100454
0.8444	Intermediate Similarity	NPC242364
0.8444	Intermediate Similarity	NPC172821
0.8444	Intermediate Similarity	NPC274446
0.8444	Intermediate Similarity	NPC485251
0.8444	Intermediate Similarity	NPC151403
0.8444	Intermediate Similarity	NPC261952
0.8444	Intermediate Similarity	NPC605171
0.8333	Intermediate Similarity	NPC69082
0.8333	Intermediate Similarity	NPC488249
0.8298	Intermediate Similarity	NPC473687
0.8298	Intermediate Similarity	NPC204686
0.8298	Intermediate Similarity	NPC219498
0.8298	Intermediate Similarity	NPC308412
0.8298	Intermediate Similarity	NPC134885
0.8298	Intermediate Similarity	NPC488247
0.8298	Intermediate Similarity	NPC210218
0.8298	Intermediate Similarity	NPC488248
0.8261	Intermediate Similarity	NPC477011
0.8125	Intermediate Similarity	NPC20621
0.8125	Intermediate Similarity	NPC318963
0.8125	Intermediate Similarity	NPC605101
0.8049	Intermediate Similarity	NPC608138
0.8043	Intermediate Similarity	NPC156804
0.8	Intermediate Similarity	NPC100921
0.8	Intermediate Similarity	NPC475159
0.8	Intermediate Similarity	NPC131002
0.8	Intermediate Similarity	NPC473780
0.8	Intermediate Similarity	NPC477018
0.8	Intermediate Similarity	NPC604521
0.78	Intermediate Similarity	NPC130359
0.78	Intermediate Similarity	NPC14901
0.7755	Intermediate Similarity	NPC134807
0.7755	Intermediate Similarity	NPC602738
0.7647	Intermediate Similarity	NPC488623
0.7647	Intermediate Similarity	NPC488624
0.7647	Intermediate Similarity	NPC488629
0.76	Intermediate Similarity	NPC473478
0.76	Intermediate Similarity	NPC473651
0.76	Intermediate Similarity	NPC20339
0.76	Intermediate Similarity	NPC66346
0.7556	Intermediate Similarity	NPC112685
0.7451	Intermediate Similarity	NPC283085
0.7451	Intermediate Similarity	NPC169511
0.7451	Intermediate Similarity	NPC287164
0.7451	Intermediate Similarity	NPC234077
0.7451	Intermediate Similarity	NPC132496
0.7358	Intermediate Similarity	NPC488630
0.7358	Intermediate Similarity	NPC488625
0.7358	Intermediate Similarity	NPC488626
0.7333	Intermediate Similarity	NPC73310
0.7333	Intermediate Similarity	NPC473529
0.7333	Intermediate Similarity	NPC180363
0.7333	Intermediate Similarity	NPC94875
0.7333	Intermediate Similarity	NPC11332
0.7333	Intermediate Similarity	NPC145914
0.7333	Intermediate Similarity	NPC601174
0.7333	Intermediate Similarity	NPC601403
0.7333	Intermediate Similarity	NPC603568
0.7333	Intermediate Similarity	NPC604330
0.7333	Intermediate Similarity	NPC608300
0.7333	Intermediate Similarity	NPC611200
0.7333	Intermediate Similarity	NPC611571
0.72	Intermediate Similarity	NPC132940
0.717	Intermediate Similarity	NPC239517
0.7143	Intermediate Similarity	NPC473649
0.7143	Intermediate Similarity	NPC473156
0.7143	Intermediate Similarity	NPC154097
0.7143	Intermediate Similarity	NPC163093
0.7143	Intermediate Similarity	NPC159750
0.7143	Intermediate Similarity	NPC73248
0.7143	Intermediate Similarity	NPC282815
0.7143	Intermediate Similarity	NPC470401
0.7143	Intermediate Similarity	NPC600956
0.7143	Intermediate Similarity	NPC610454
0.7115	Intermediate Similarity	NPC231096
0.7115	Intermediate Similarity	NPC475581
0.7115	Intermediate Similarity	NPC62118
0.7115	Intermediate Similarity	NPC107717
0.7115	Intermediate Similarity	NPC488252
0.7115	Intermediate Similarity	NPC606740
0.7115	Intermediate Similarity	NPC608614
0.7059	Intermediate Similarity	NPC309211
0.7059	Intermediate Similarity	NPC329838
0.7059	Intermediate Similarity	NPC20533
0.7059	Intermediate Similarity	NPC477010
0.7037	Intermediate Similarity	NPC91067
0.7	Intermediate Similarity	NPC473671
0.7	Intermediate Similarity	NPC475268
0.7	Intermediate Similarity	NPC470400
0.7	Intermediate Similarity	NPC77871
0.7	Intermediate Similarity	NPC9678
0.7	Intermediate Similarity	NPC319036
0.7	Intermediate Similarity	NPC604764
0.7	Intermediate Similarity	NPC605867
0.6981	Remote Similarity	NPC233551
0.6981	Remote Similarity	NPC40376
0.6981	Remote Similarity	NPC21208
0.6875	Remote Similarity	NPC329829
0.6792	Remote Similarity	NPC258068
0.6792	Remote Similarity	NPC476583
0.6786	Remote Similarity	NPC473663
0.6786	Remote Similarity	NPC473723
0.6786	Remote Similarity	NPC475173
0.6727	Remote Similarity	NPC480081
0.6667	Remote Similarity	NPC480079
0.6667	Remote Similarity	NPC477014
0.6667	Remote Similarity	NPC477013
0.6531	Remote Similarity	NPC25764
0.6531	Remote Similarity	NPC235809
0.6531	Remote Similarity	NPC39279
0.6531	Remote Similarity	NPC39167
0.6531	Remote Similarity	NPC292809
0.6531	Remote Similarity	NPC202055
0.6531	Remote Similarity	NPC606804
0.6531	Remote Similarity	NPC607425
0.6531	Remote Similarity	NPC608574
0.6471	Remote Similarity	NPC488246
0.6471	Remote Similarity	NPC144415
0.6471	Remote Similarity	NPC480080
0.6471	Remote Similarity	NPC607439
0.6471	Remote Similarity	NPC608157
0.6364	Remote Similarity	NPC89001
0.6346	Remote Similarity	NPC241360
0.6346	Remote Similarity	NPC293136
0.6296	Remote Similarity	NPC473707
0.6271	Remote Similarity	NPC482766
0.6271	Remote Similarity	NPC279267
0.6226	Remote Similarity	NPC473904
0.6182	Remote Similarity	NPC120398
0.6182	Remote Similarity	NPC471567
0.6154	Remote Similarity	NPC600524
0.6154	Remote Similarity	NPC608355
0.614	Remote Similarity	NPC280612
0.6038	Remote Similarity	NPC219652
0.6038	Remote Similarity	NPC473840
0.6	Remote Similarity	NPC11456
0.6	Remote Similarity	NPC477012
0.6	Remote Similarity	NPC477017
0.6	Remote Similarity	NPC477016
0.5926	Remote Similarity	NPC65930
0.5818	Remote Similarity	NPC485250
0.5818	Remote Similarity	NPC605396
0.5741	Remote Similarity	NPC25703
0.5714	Remote Similarity	NPC139418
0.5636	Remote Similarity	NPC480251
0.5636	Remote Similarity	NPC480250
0.5614	Remote Similarity	NPC473995
0.5614	Remote Similarity	NPC488244
0.5556	Remote Similarity	NPC482767
0.5556	Remote Similarity	NPC475260
0.5556	Remote Similarity	NPC488621
0.5556	Remote Similarity	NPC473775
0.5556	Remote Similarity	NPC488622

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473669 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6261
0.1-0.2	2820
0.2-0.3	69
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