NPASS Compound

Natural Product: NPC473529

Natural Product ID	NPC473529
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Reticulatacin
IUPAC Name	4-[(15S)-15-hydroxy-15-[(2S,5S)-5-[(1S)-1-hydroxytridecyl]oxolan-2-yl]pentadecyl]-2-methyl-2H-furan-5-one
Synonyms	Reticulatacin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL444743
PubChem CID	10438442
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 110111 0 0 0 0 0 0 0 0999 V2000 -14.1041 -0.0096 1.8766 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.7540 -0.0272 1.1807 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.3252 -1.4106 0.8195 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9980 -1.3750 0.1198 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8775 -0.7802 0.9491 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5938 -0.7914 0.1337 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4701 -0.2090 0.9292 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6558 1.1818 1.3984 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9496 2.2636 0.4885 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1286 2.6921 -0.6451 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7367 3.1091 -0.4505 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6887 2.1364 -0.1014 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3974 1.1302 -1.1913 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3229 0.1768 -0.7247 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8685 -0.7055 -1.8433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4735 -0.1429 -2.1630 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4573 1.1091 -1.3745 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2261 0.8835 -0.2711 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1853 1.8234 -1.1381 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7302 1.3635 -0.0733 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2290 -0.0295 -0.2766 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9627 -0.2047 -1.5709 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4765 -1.5860 -1.8181 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4357 -1.9412 -0.6937 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0081 -3.3402 -0.9099 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9407 -3.6332 0.2319 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0756 -2.6612 0.3733 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9045 -2.6288 -0.8614 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0896 -1.6564 -0.7469 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6439 -0.2722 -0.5001 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5969 0.8408 -0.4666 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7205 0.8992 0.4732 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7986 -0.1219 0.3355 C 0 0 0 0 0 0 0 0 0 0 0 0 11.8681 0.1201 1.3790 C 0 0 0 0 0 0 0 0 0 0 0 0 13.1364 0.3722 1.1711 C 0 0 0 0 0 0 0 0 0 0 0 0 13.8326 0.5438 2.4585 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8623 0.3798 3.4323 O 0 0 0 0 0 0 0 0 0 0 0 0 11.6553 0.1168 2.8124 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5771 -0.0842 3.4626 O 0 0 0 0 0 0 0 0 0 0 0 0 14.3089 1.9932 2.4967 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5687 3.1527 -0.6856 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5208 0.4858 -1.6521 O 0 0 0 0 0 0 0 0 0 0 0 0 -14.2922 -0.8832 2.5001 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.1462 0.8972 2.5115 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.9009 0.1436 1.0921 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8166 0.5784 0.2392 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0285 0.4650 1.8397 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.0573 -1.8447 0.1025 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2166 -2.0482 1.7233 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7598 -2.4323 -0.1649 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0337 -0.7932 -0.8393 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1148 0.2538 1.2669 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7807 -1.3921 1.8667 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3640 -1.8840 -0.0415 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7210 -0.3579 -0.8559 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4647 -0.8288 1.9224 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5083 -0.4774 0.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5180 1.1378 2.1571 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7862 1.3976 2.1019 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1963 3.1780 1.1616 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9886 2.0420 0.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6616 3.6379 -1.0596 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2647 1.9264 -1.4616 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7417 3.8800 0.3970 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3520 3.7473 -1.3147 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8956 1.5731 0.8167 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7585 2.7314 0.1422 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9652 1.6474 -2.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7513 -0.4301 0.1199 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8289 -1.7775 -1.5641 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4899 -0.5213 -2.7386 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4130 0.0602 -3.2764 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7770 -0.9377 -1.8840 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0337 1.8579 -2.0709 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2979 2.0140 -2.1139 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5664 2.0837 0.1225 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1486 1.3419 0.8993 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0229 -0.1506 0.5666 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4354 -0.7463 -0.0543 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3703 0.1464 -2.4458 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8828 0.4558 -1.5348 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6176 -2.2745 -1.8577 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9824 -1.6570 -2.8030 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8635 -1.9758 0.2304 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3076 -1.2544 -0.6836 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1534 -4.0594 -0.9358 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5201 -3.3178 -1.8930 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3517 -4.6719 0.0852 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3908 -3.6372 1.1944 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7207 -1.6634 0.6846 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6670 -3.0299 1.2643 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3630 -3.6374 -1.0088 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3163 -2.4048 -1.7619 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5780 -2.0273 0.2107 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7541 -1.8423 -1.5713 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8162 0.0332 -1.2359 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0567 -0.2205 0.4861 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9594 1.7811 -0.2567 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9739 1.0836 -1.5242 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2244 1.9278 0.4457 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2879 0.8956 1.5232 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5290 -1.1676 0.3284 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2637 0.0653 -0.6875 H 0 0 0 0 0 0 0 0 0 0 0 0 13.5689 0.4361 0.1569 H 0 0 0 0 0 0 0 0 0 0 0 0 14.6974 -0.1524 2.5654 H 0 0 0 0 0 0 0 0 0 0 0 0 15.2262 2.1111 3.1014 H 0 0 0 0 0 0 0 0 0 0 0 0 13.4797 2.6598 2.8069 H 0 0 0 0 0 0 0 0 0 0 0 0 14.5719 2.2814 1.4527 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4699 3.3580 -1.0021 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4188 -0.4937 -1.7742 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 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 2 0 36 40 1 0 19 41 1 0 13 42 1 0 18 14 1 0 38 34 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 0 14 69 1 0 15 70 1 0 15 71 1 0 16 72 1 0 16 73 1 0 17 74 1 0 19 75 1 0 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 27 91 1 0 28 92 1 0 28 93 1 0 29 94 1 0 29 95 1 0 30 96 1 0 30 97 1 0 31 98 1 0 31 99 1 0 32100 1 0 32101 1 0 33102 1 0 33103 1 0 35104 1 0 36105 1 0 40106 1 0 40107 1 0 40108 1 0 41109 1 0 42110 1 0 M END

Standard InCHIKey	BDGWQMLWIGDEKO-TZYWOTFASA-N
Standard InCHI	InChI=1S/C37H68O5/c1-3-4-5-6-7-8-14-17-20-23-26-33(38)35-28-29-36(42-35)34(39)27-24-21-18-15-12-10-9-11-13-16-19-22-25-32-30-31(2)41-37(32)40/h30-31,33-36,38-39H,3-29H2,1-2H3/t31?,33-,34-,35-,36-/m0/s1
SMILES	CCCCCCCCCCCCC(C1CCC(O1)C(CCCCCCCCCCCCCCC2=CC(OC2=O)C)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.51	Volume:	670.073 ? Van der Waals volume.
Dense:	0.884	LogP:	9.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.935 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.654 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	28.0	Rigid Bonds:	11.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.07	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.226	Fsp³:	0.919
MCE-18:	27.831 ? 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:	0.652	Fluc inhibitor:	0.264 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.031 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.504	Promiscuous compounds:	0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.138	MDCK Permeability:	-4.836
Pgp-inhibitor:	0.0	Pgp-substrate:	0.069
PAMPA:	0.003 ? 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):	1.0
20% Bioavailability (F20%):	0.998	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.997
Plasma Protein Binding (PPB):	99.637%	Volume Distribution (VD):	1.399
Fu:	0.988% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.075
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.668
BSEP inhibitor:	0.573

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.502
CYP2C19-inhibitor:	0.579	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.492	CYP2D6-substrate:	0.892
CYP3A4-inhibitor:	0.214	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	0.956
HLM stability:	0.017 ? 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):

4.984

Half-life (T1/2):

2.475

ADMET: Toxicity

hERG Blockers:	0.866	hERG Blockers (10um):	0.969
Human Hepatotoxicity (H-HT):	0.569	Drug-induced Liver Injury (DILI):	0.14
AMES Toxicity:	0.049	Rat Oral Acute Toxicity:	0.204
Maximum Recommended Daily Dose:	0.594	Skin Sensitization:	1.0
Carcinogencity:	0.096	Eye Corrosion:	0.001
Eye Irritation:	0.269	Respiratory Toxicity:	0.797
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.592
Hematotoxicity:	0.025	Drug-induced Nephrotoxicity:	0.376
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.076
A549 Cytotoxicity:	0.948	Hek293 Cytotoxicity:	0.573
BCF:	0.299 ? 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:	4.936 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.747 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.756 ? 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
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1021/np50053a043]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8277309]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	Bark	n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9632	Annona reticulata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9632	Annona reticulata	Species	Annonaceae	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
ED50	3

Activity Type	# Activity
Cell line	3

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	=	3.49	ug ml-1	PMID[22348826]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	2.91	ug ml-1	PMID[9622558]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	4.66	ug ml-1	PMID[26105195]

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 NPC473529 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	14644
0.1-0.2	30209
0.2-0.3	4561
0.3-0.4	205
0.4-0.5	33
0.5-0.6	25
0.6-0.7	70
0.7-0.8	0
0.8-0.85	17
0.85-0.9	14
0.9-0.95	5
0.95-1	12

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC73310
1.0	High Similarity	NPC180363
1.0	High Similarity	NPC94875
1.0	High Similarity	NPC11332
1.0	High Similarity	NPC145914
1.0	High Similarity	NPC601174
1.0	High Similarity	NPC601403
1.0	High Similarity	NPC603568
1.0	High Similarity	NPC604330
1.0	High Similarity	NPC608300
1.0	High Similarity	NPC611200
1.0	High Similarity	NPC611571
0.925	High Similarity	NPC329829
0.925	High Similarity	NPC475159
0.925	High Similarity	NPC131002
0.925	High Similarity	NPC473780
0.925	High Similarity	NPC604521
0.881	High Similarity	NPC156804
0.878	High Similarity	NPC25764
0.878	High Similarity	NPC235809
0.878	High Similarity	NPC39279
0.878	High Similarity	NPC39167
0.878	High Similarity	NPC292809
0.878	High Similarity	NPC202055
0.878	High Similarity	NPC606804
0.878	High Similarity	NPC607425
0.878	High Similarity	NPC608574
0.8605	High Similarity	NPC163093
0.8605	High Similarity	NPC144415
0.8605	High Similarity	NPC607439
0.8605	High Similarity	NPC608157
0.8409	Intermediate Similarity	NPC241360
0.8409	Intermediate Similarity	NPC293136
0.8333	Intermediate Similarity	NPC100921
0.8333	Intermediate Similarity	NPC477018
0.8182	Intermediate Similarity	NPC473156
0.8182	Intermediate Similarity	NPC282815
0.8182	Intermediate Similarity	NPC600956
0.8043	Intermediate Similarity	NPC329838
0.8	Intermediate Similarity	NPC473671
0.8	Intermediate Similarity	NPC219652
0.8	Intermediate Similarity	NPC475268
0.8	Intermediate Similarity	NPC473840
0.8	Intermediate Similarity	NPC470400
0.8	Intermediate Similarity	NPC77871
0.8	Intermediate Similarity	NPC9678
0.8	Intermediate Similarity	NPC319036
0.8	Intermediate Similarity	NPC605867
0.7826	Intermediate Similarity	NPC65930
0.7826	Intermediate Similarity	NPC132940
0.7778	Intermediate Similarity	NPC610454
0.7708	Intermediate Similarity	NPC258068
0.7708	Intermediate Similarity	NPC476583
0.7674	Intermediate Similarity	NPC606043
0.766	Intermediate Similarity	NPC20533
0.766	Intermediate Similarity	NPC485250
0.766	Intermediate Similarity	NPC605396
0.7609	Intermediate Similarity	NPC25703
0.7551	Intermediate Similarity	NPC477014
0.7551	Intermediate Similarity	NPC477013
0.75	Intermediate Similarity	NPC107986
0.75	Intermediate Similarity	NPC223871
0.75	Intermediate Similarity	NPC231009
0.75	Intermediate Similarity	NPC103284
0.75	Intermediate Similarity	NPC110710
0.75	Intermediate Similarity	NPC1083
0.75	Intermediate Similarity	NPC82795
0.75	Intermediate Similarity	NPC286338
0.75	Intermediate Similarity	NPC603931
0.75	Intermediate Similarity	NPC604237
0.75	Intermediate Similarity	NPC609415
0.7391	Intermediate Similarity	NPC473649
0.7391	Intermediate Similarity	NPC154097
0.7391	Intermediate Similarity	NPC159750
0.7391	Intermediate Similarity	NPC73248
0.7391	Intermediate Similarity	NPC470401
0.7391	Intermediate Similarity	NPC600524
0.7391	Intermediate Similarity	NPC608355
0.7347	Intermediate Similarity	NPC120398
0.7347	Intermediate Similarity	NPC473995
0.7347	Intermediate Similarity	NPC471567
0.7333	Intermediate Similarity	NPC488253
0.7333	Intermediate Similarity	NPC473669
0.7333	Intermediate Similarity	NPC488251
0.7292	Intermediate Similarity	NPC309211
0.7292	Intermediate Similarity	NPC329615
0.7292	Intermediate Similarity	NPC477010
0.7234	Intermediate Similarity	NPC604764
0.7174	Intermediate Similarity	NPC232555
0.7174	Intermediate Similarity	NPC171174
0.7174	Intermediate Similarity	NPC114694
0.7174	Intermediate Similarity	NPC485248
0.7174	Intermediate Similarity	NPC142117
0.7174	Intermediate Similarity	NPC480249
0.7174	Intermediate Similarity	NPC485249
0.7174	Intermediate Similarity	NPC240695
0.7143	Intermediate Similarity	NPC477012
0.7115	Intermediate Similarity	NPC477015
0.7021	Intermediate Similarity	NPC488632
0.7021	Intermediate Similarity	NPC134865
0.7021	Intermediate Similarity	NPC103523
0.7021	Intermediate Similarity	NPC488627
0.7021	Intermediate Similarity	NPC488631
0.7021	Intermediate Similarity	NPC477011
0.6923	Remote Similarity	NPC473520
0.6923	Remote Similarity	NPC280612
0.6875	Remote Similarity	NPC280621
0.6875	Remote Similarity	NPC48338
0.6875	Remote Similarity	NPC488628
0.6863	Remote Similarity	NPC320458
0.6863	Remote Similarity	NPC480082
0.6809	Remote Similarity	NPC81045
0.6809	Remote Similarity	NPC39754
0.6809	Remote Similarity	NPC171135
0.6809	Remote Similarity	NPC182383
0.6809	Remote Similarity	NPC61257
0.6809	Remote Similarity	NPC320569
0.6809	Remote Similarity	NPC133730
0.6809	Remote Similarity	NPC191929
0.6809	Remote Similarity	NPC100454
0.6809	Remote Similarity	NPC242364
0.6809	Remote Similarity	NPC172821
0.6809	Remote Similarity	NPC274446
0.6809	Remote Similarity	NPC485251
0.6809	Remote Similarity	NPC151403
0.6809	Remote Similarity	NPC261952
0.6809	Remote Similarity	NPC605171
0.6792	Remote Similarity	NPC473905
0.6792	Remote Similarity	NPC253801
0.6735	Remote Similarity	NPC178215
0.6735	Remote Similarity	NPC473687
0.6735	Remote Similarity	NPC204686
0.6735	Remote Similarity	NPC219498
0.6735	Remote Similarity	NPC308412
0.6735	Remote Similarity	NPC134885
0.6735	Remote Similarity	NPC488247
0.6735	Remote Similarity	NPC210218
0.6735	Remote Similarity	NPC488248
0.6667	Remote Similarity	NPC93794
0.6667	Remote Similarity	NPC473504
0.6667	Remote Similarity	NPC81778
0.6667	Remote Similarity	NPC40066
0.66	Remote Similarity	NPC20621
0.66	Remote Similarity	NPC318963
0.66	Remote Similarity	NPC134807
0.66	Remote Similarity	NPC488250
0.66	Remote Similarity	NPC605101
0.6538	Remote Similarity	NPC89001
0.6471	Remote Similarity	NPC69082
0.6471	Remote Similarity	NPC488249
0.64	Remote Similarity	NPC42598
0.6346	Remote Similarity	NPC130359
0.6346	Remote Similarity	NPC14901
0.6327	Remote Similarity	NPC47937
0.6296	Remote Similarity	NPC322529
0.6275	Remote Similarity	NPC602738
0.6226	Remote Similarity	NPC488623
0.6226	Remote Similarity	NPC488624
0.6226	Remote Similarity	NPC488629
0.6216	Remote Similarity	NPC84038
0.6154	Remote Similarity	NPC473478
0.6154	Remote Similarity	NPC473651
0.6154	Remote Similarity	NPC66346
0.614	Remote Similarity	NPC477017
0.614	Remote Similarity	NPC477016
0.6078	Remote Similarity	NPC478998
0.6038	Remote Similarity	NPC283085
0.6038	Remote Similarity	NPC169511
0.6038	Remote Similarity	NPC287164
0.6038	Remote Similarity	NPC234077
0.6038	Remote Similarity	NPC132496
0.6	Remote Similarity	NPC488630
0.6	Remote Similarity	NPC488625
0.6	Remote Similarity	NPC488626
0.5957	Remote Similarity	NPC112685
0.5909	Remote Similarity	NPC608138
0.5818	Remote Similarity	NPC239517
0.5741	Remote Similarity	NPC231096
0.5741	Remote Similarity	NPC475581
0.5741	Remote Similarity	NPC62118
0.5741	Remote Similarity	NPC107717
0.5741	Remote Similarity	NPC488252
0.5741	Remote Similarity	NPC606740
0.5741	Remote Similarity	NPC608614
0.5714	Remote Similarity	NPC91067
0.566	Remote Similarity	NPC600188
0.5636	Remote Similarity	NPC233551
0.5636	Remote Similarity	NPC40376
0.5636	Remote Similarity	NPC21208
0.5556	Remote Similarity	NPC20339
0.5517	Remote Similarity	NPC473663
0.5517	Remote Similarity	NPC473723
0.5517	Remote Similarity	NPC475173
0.5476	Remote Similarity	NPC218477
0.5476	Remote Similarity	NPC474705
0.5476	Remote Similarity	NPC186531
0.5439	Remote Similarity	NPC480081
0.5366	Remote Similarity	NPC609089
0.5273	Remote Similarity	NPC139418

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473529 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6021
0.1-0.2	3003
0.2-0.3	122
0.3-0.4	4
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