NPASS Compound

Natural Product: NPC485966

Natural Product ID	NPC485966
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PYIDSJMLYRYDMC-ILPWDNDNSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 107115 0 0 0 0 0 0 0 0999 V2000 -1.4557 -6.2938 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0507 -6.8191 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3543 -7.3444 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4949 -8.3186 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9089 -7.8178 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.0495 -8.7920 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3529 -6.3746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1698 -5.1166 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8580 -3.6494 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0237 -2.7054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5052 -2.9400 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4492 -1.7743 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9117 -0.3739 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4301 -0.1393 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4861 -1.3050 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9882 -1.3835 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.6000 -2.8324 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 -3.1443 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3158 -4.4023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6277 -5.8695 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8857 -6.6865 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5667 -8.0230 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9091 -9.3712 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0646 -8.1015 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7456 -9.4380 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 -2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 -3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 -3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2841 1.5763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 3.0703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3344 4.1069 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.9033 5.4949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9857 6.6815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5008 6.4801 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0696 5.0922 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0788 3.9825 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0881 2.8728 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1885 4.9917 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1520 3.9056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9214 2.6179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0484 4.1125 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4153 2.7523 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1228 1.4297 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0459 4.1134 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5398 4.2478 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0967 -5.1517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2114 -6.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8607 -5.7684 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1484 -7.6243 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2860 -4.8034 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6420 -5.4886 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5760 -8.2241 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5930 -8.6368 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3375 -9.2727 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8957 -9.7640 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9205 -10.0132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1554 -7.7787 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0753 -9.9326 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5891 -7.2241 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5064 -4.4356 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1735 -6.2313 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0428 -4.3404 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9307 -2.0090 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8556 0.7918 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8926 1.2611 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1934 -0.1114 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2113 -1.6463 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0723 -5.2411 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0722 -3.5636 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2971 -6.5621 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0469 -7.9301 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4266 -10.7745 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0821 -8.7570 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5020 -10.2768 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 -4.2246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 -1.2902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8112 0.1720 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7840 1.5950 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8911 2.7841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3392 4.2546 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9125 6.6046 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2596 4.8542 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5545 8.0694 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9664 6.7993 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4409 7.9789 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2306 6.0420 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2463 2.7347 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2251 1.8944 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4858 3.4172 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9784 1.8635 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6861 5.0778 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3115 5.3321 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4983 3.7278 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1250 5.1570 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7648 0.1828 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0338 4.3823 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4054 5.7418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6743 2.7539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1955 -7.2875 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6740 -7.5558 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2151 -5.0406 0.0000 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 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 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 1 0 22 23 2 0 22 24 1 0 24 25 1 0 18 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 39 41 1 0 38 42 1 0 42 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 46 47 1 0 43 48 1 0 48 49 2 0 48 50 1 0 50 51 1 0 27 52 1 0 52 53 1 0 20 3 1 0 47 26 2 0 21 7 1 0 47 30 1 0 17 9 2 0 45 31 2 0 15 10 1 0 42 34 1 0 44 36 1 0 1 54 1 0 1 55 1 0 1 56 1 0 2 57 1 0 2 58 1 0 3 59 1 1 4 60 1 0 4 61 1 0 6 62 1 0 6 63 1 0 6 64 1 0 7 65 1 1 8 66 1 0 8 67 1 0 11 68 1 0 12 69 1 0 13 70 1 0 14 71 1 0 16 72 1 0 18 73 1 6 19 74 1 0 19 75 1 0 20 76 1 1 21 77 1 0 25 78 1 0 25 79 1 0 25 80 1 0 28 81 1 0 29 82 1 0 32 83 1 0 32 84 1 0 33 85 1 0 33 86 1 0 35 87 1 0 35 88 1 0 36 89 1 6 37 90 1 0 37 91 1 0 38 92 1 1 39 93 1 6 40 94 1 0 40 95 1 0 40 96 1 0 41 97 1 0 42 98 1 6 44 99 1 0 44100 1 0 46101 1 0 51102 1 0 51103 1 0 51104 1 0 53105 1 0 53106 1 0 53107 1 0 M END

Standard InCHIKey	PYIDSJMLYRYDMC-ILPWDNDNSA-N
Standard InCHI	InChI=1S/C43H54N4O6/c1-7-24-21-46(3)33-18-30-25-10-8-9-11-32(25)44-37(30)31(17-29(24)35(33)41(49)52-5)36-34(51-4)13-12-26-27-14-15-47-20-23-16-28(22(2)48)40(47)43(19-23,42(50)53-6)39(27)45-38(26)36/h8-13,22-24,28-29,31,33,35,40,44-45,48H,7,14-21H2,1-6H3/t22-,23-,24-,28+,29-,31-,33-,35?,40-,43?/m0/s1
SMILES	CC[C@H]1CN(C)[C@H]2Cc3c4ccccc4[nH]c3[C@@H](C[C@@H]1C2C(=O)OC)c1c(ccc2c3CCN4C[C@H]5C[C@H]([C@H](C)O)[C@H]4C(C5)(c3[nH]c12)C(=O)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	722.4	Volume:	745.64 ? Van der Waals volume.
Dense:	0.969	LogP:	4.294 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.319 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.861 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	46.0
TPSA:	120.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	3.0	Rings:	10.0
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:	6.706	Fsp³:	0.581
MCE-18:	185.5 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.946	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.876 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.299 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.642

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.305	MDCK Permeability:	-5.026
Pgp-inhibitor:	0.01	Pgp-substrate:	0.887
PAMPA:	0.005 ? 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%):	0.429	30% Bioavailability (F30%):	0.971
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.18	MRP1:	1.0
Plasma Protein Binding (PPB):	84.15%	Volume Distribution (VD):	0.203
Fu:	11.245% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.764
OATP1B3 inhibitor:	0.723	BCRP inhibitor:	0.969
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.876
HLM stability:	0.993 ? 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):

10.867

Half-life (T1/2):

1.439

ADMET: Toxicity

hERG Blockers:	0.916	hERG Blockers (10um):	0.625
Human Hepatotoxicity (H-HT):	0.936	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.919	Rat Oral Acute Toxicity:	0.991
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	0.989
Carcinogencity:	0.773	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.999
Drug-induced Neurotoxicity:	0.993	Ototoxicity:	0.985
Hematotoxicity:	0.895	Drug-induced Nephrotoxicity:	0.999
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.373
A549 Cytotoxicity:	0.998	Hek293 Cytotoxicity:	0.983
BCF:	0.938 ? 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:	4.205 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.675 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.311 ? 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
NPO32684	tabernaemontana elegans	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[19473031]
NPO32684	tabernaemontana elegans	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27704811]

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	8
IC50	2
FC	3

Activity Type	# Activity
Cell line	13

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
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	39.3	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	42.3	%	PMID[27704811]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	8400.0	nM	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	19.3	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	55.0	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	18.5	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	15.7	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	FC	=	2.5	n.a.	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	11.0	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	13.0	%	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	FC	=	1.6	n.a.	PMID[27704811]
NPT393	Cell line	HCT-116	Homo sapiens	FC	=	1.5	n.a.	PMID[27704811]

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 NPC485966 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	22269
0.1-0.2	26821
0.2-0.3	595
0.3-0.4	97
0.4-0.5	30
0.5-0.6	21
0.6-0.7	11
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.901	High Similarity	NPC485969
0.8224	Intermediate Similarity	NPC81939
0.7611	Intermediate Similarity	NPC485922
0.7387	Intermediate Similarity	NPC17437
0.7321	Intermediate Similarity	NPC485933
0.7321	Intermediate Similarity	NPC485970
0.7304	Intermediate Similarity	NPC485886
0.7091	Intermediate Similarity	NPC485963
0.6777	Remote Similarity	NPC488882
0.6777	Remote Similarity	NPC485918
0.6777	Remote Similarity	NPC485915
0.6667	Remote Similarity	NPC475666
0.6465	Remote Similarity	NPC485936
0.6465	Remote Similarity	NPC485937
0.6387	Remote Similarity	NPC485890
0.6333	Remote Similarity	NPC485967
0.622	Remote Similarity	NPC471303
0.6142	Remote Similarity	NPC485935
0.6	Remote Similarity	NPC485964
0.5968	Remote Similarity	NPC485885
0.5865	Remote Similarity	NPC473105
0.5846	Remote Similarity	NPC485943
0.5814	Remote Similarity	NPC485912
0.5738	Remote Similarity	NPC485894
0.5686	Remote Similarity	NPC329858
0.566	Remote Similarity	NPC474192
0.553	Remote Similarity	NPC488883
0.5455	Remote Similarity	NPC485962
0.5455	Remote Similarity	NPC477065
0.5455	Remote Similarity	NPC605382
0.5429	Remote Similarity	NPC482061
0.5368	Remote Similarity	NPC485910
0.5267	Remote Similarity	NPC485913
0.5267	Remote Similarity	NPC485889
0.5255	Remote Similarity	NPC485907
0.5255	Remote Similarity	NPC485906
0.5182	Remote Similarity	NPC485911
0.5154	Remote Similarity	NPC485891
0.514	Remote Similarity	NPC473041
0.5115	Remote Similarity	NPC485968

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485966 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4550
0.1-0.2	4504
0.2-0.3	79
0.3-0.4	15
0.4-0.5	1
0.5-0.6	0
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
0.6179	Remote Similarity	NPD8358	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