NPASS Compound

Natural Product: NPC319036

Natural Product ID	NPC319036
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Rel-Annosquacin-I
IUPAC Name	(2S)-4-[(8R)-8-[(2R,5R)-5-[(2R,5R)-5-[(1S)-1,5-dihydroxyhexadecyl]oxolan-2-yl]oxolan-2-yl]-8-hydroxyoctyl]-2-methyl-2H-furan-5-one
Synonyms	Rel-Annosquacin-I
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1933122
PubChem CID	56655644
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 110112 0 0 0 0 0 0 0 0999 V2000 -10.2951 5.4400 1.1920 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.0438 4.2379 0.7187 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0514 3.4603 -0.2051 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7286 2.2624 -0.6956 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1681 1.3186 -1.6538 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9503 0.5585 -1.5096 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5807 1.0420 -1.5680 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0746 2.0615 -0.6562 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5675 2.2946 -0.8910 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7634 1.0484 -0.6775 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8942 0.4993 0.7156 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0780 -0.7645 0.8298 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6287 -0.5508 0.5610 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7961 -1.8211 0.6606 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8387 -2.4672 1.9938 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0608 -3.7465 2.1208 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4109 -3.6325 1.8700 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9352 -5.0862 1.8404 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7501 -5.3431 0.3664 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1681 -4.0463 -0.2224 C 0 0 1 0 0 0 0 0 0 0 0 0 0.6792 -3.1075 0.6568 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6586 -3.8696 -0.3329 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3326 -4.8372 -1.2189 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7069 -4.0043 -2.4231 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9129 -2.6717 -1.7378 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9166 -2.5966 -0.7720 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2435 -2.6056 -1.0232 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4102 -2.6762 -1.9398 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6918 -2.6349 -1.1638 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9415 -1.4077 -0.3547 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0226 -0.1465 -1.1615 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2801 1.0507 -0.3248 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2208 1.3361 0.6824 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5554 2.5702 1.5108 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7192 3.7824 0.7120 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8566 4.4945 0.6843 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6508 5.6355 -0.2196 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3272 5.5192 -0.7210 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7392 4.4004 -0.1598 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5646 3.9591 -0.3443 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7253 6.9213 0.5974 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2468 -1.3751 -0.3514 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3098 -4.3318 3.3877 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5725 -1.6703 -0.1178 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.7152 5.8546 0.3509 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5324 5.1189 1.9519 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9487 6.2338 1.5985 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9249 4.5293 0.1486 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3195 3.5331 1.4997 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2378 3.1925 0.5319 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6753 4.1807 -0.9356 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8170 2.5510 -1.0229 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0139 1.6560 0.2549 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1645 1.8792 -2.6906 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0600 0.5935 -1.9153 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0149 -0.1096 -0.5533 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0394 -0.3087 -2.2946 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3492 1.4210 -2.6434 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9078 0.1180 -1.4425 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4870 3.0735 -0.9753 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2323 1.8743 0.3985 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4157 2.6078 -1.9432 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2306 3.0817 -0.2196 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8970 0.2833 -1.4662 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6837 1.3800 -0.7638 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9389 0.3607 0.9820 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4478 1.2617 1.4094 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2185 -1.1604 1.8677 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1526 0.1920 1.2027 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4940 -0.2104 -0.4956 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2274 -2.5371 -0.0906 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7831 -1.5379 0.2960 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9191 -2.6448 2.2582 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4615 -1.6934 2.7345 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5532 -4.4669 1.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8990 -3.0950 2.7234 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3469 -5.7361 2.4916 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9829 -5.0135 2.1580 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2947 -6.2241 0.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3136 -5.5100 0.1742 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6643 -3.8752 -1.2079 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0994 -3.9503 0.7040 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2988 -5.1622 -0.7464 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7393 -5.7276 -1.4877 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7753 -3.9134 -3.0397 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5686 -4.3704 -2.9710 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7812 -1.8692 -2.4709 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2935 -3.4448 -0.3204 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3941 -1.8706 -2.7234 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4160 -3.6794 -2.4642 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5810 -2.7250 -1.8650 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7927 -3.5348 -0.5159 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3334 -1.3408 0.5520 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0032 -1.5478 0.0519 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9372 -0.2835 -1.8243 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1180 -0.0213 -1.7799 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4109 1.9208 -1.0361 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2999 0.9628 0.1588 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0833 0.4597 1.3391 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2901 1.5945 0.1303 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4774 2.3017 2.0740 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7815 2.7531 2.2855 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7680 4.2923 1.2143 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3566 5.6745 -1.0752 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2502 7.6806 -0.0250 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3702 6.6939 1.4797 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7061 7.1974 0.8893 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5223 -1.3552 0.3384 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2289 -4.1433 3.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4947 -1.9446 0.0727 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 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 25 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 1 0 35 36 2 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 37 41 1 0 27 42 1 0 16 43 1 0 12 44 1 0 21 17 1 0 26 22 1 0 39 35 1 0 1 45 1 0 1 46 1 0 1 47 1 0 2 48 1 0 2 49 1 0 3 50 1 0 3 51 1 0 4 52 1 0 4 53 1 0 5 54 1 0 5 55 1 0 6 56 1 0 6 57 1 0 7 58 1 0 7 59 1 0 8 60 1 0 8 61 1 0 9 62 1 0 9 63 1 0 10 64 1 0 10 65 1 0 11 66 1 0 11 67 1 0 12 68 1 0 13 69 1 0 13 70 1 0 14 71 1 0 14 72 1 0 15 73 1 0 15 74 1 0 16 75 1 6 17 76 1 1 18 77 1 0 18 78 1 0 19 79 1 0 19 80 1 0 20 81 1 6 22 82 1 1 23 83 1 0 23 84 1 0 24 85 1 0 24 86 1 0 25 87 1 6 27 88 1 1 28 89 1 0 28 90 1 0 29 91 1 0 29 92 1 0 30 93 1 0 30 94 1 0 31 95 1 0 31 96 1 0 32 97 1 0 32 98 1 0 33 99 1 0 33100 1 0 34101 1 0 34102 1 0 36103 1 0 37104 1 6 41105 1 0 41106 1 0 41107 1 0 42108 1 0 43109 1 0 44110 1 0 M END

Standard InCHIKey	GHKXYVAVEAMUNF-SWWNTVRDSA-N
Standard InCHI	InChI=1S/C37H66O7/c1-3-4-5-6-7-8-9-12-15-19-30(38)20-17-22-32(40)34-24-26-36(44-34)35-25-23-33(43-35)31(39)21-16-13-10-11-14-18-29-27-28(2)42-37(29)41/h27-28,30-36,38-40H,3-26H2,1-2H3/t28-,30?,31+,32-,33+,34+,35+,36+/m0/s1
SMILES	CCCCCCCCCCCC(CCC[C@@H]([C@H]1CC[C@@H](O1)[C@H]1CC[C@@H](O1)[C@@H](CCCCCCCC1=C[C@@H](OC1=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	622.48	Volume:	679.097 ? Van der Waals volume.
Dense:	0.917	LogP:	5.555 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.895 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.709 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	25.0	Rigid Bonds:	16.0
TPSA:	105.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

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:	4.782	Fsp³:	0.919
MCE-18:	42.817 ? 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:	0.866	Fluc inhibitor:	0.023 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.087 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.549	Promiscuous compounds:	0.227

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.195	MDCK Permeability:	-4.816
Pgp-inhibitor:	0.069	Pgp-substrate:	0.971
PAMPA:	0.014 ? 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):	0.405
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.98
Plasma Protein Binding (PPB):	96.751%	Volume Distribution (VD):	0.454
Fu:	2.948% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.58
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.848
BSEP inhibitor:	0.831

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.15
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.85	CYP2C9-substrate:	0.029
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.467
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.001 ? 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):

5.415

Half-life (T1/2):

1.289

ADMET: Toxicity

hERG Blockers:	0.611	hERG Blockers (10um):	0.862
Human Hepatotoxicity (H-HT):	0.73	Drug-induced Liver Injury (DILI):	0.166
AMES Toxicity:	0.329	Rat Oral Acute Toxicity:	0.109
Maximum Recommended Daily Dose:	0.869	Skin Sensitization:	1.0
Carcinogencity:	0.258	Eye Corrosion:	0.025
Eye Irritation:	0.583	Respiratory Toxicity:	0.937
Drug-induced Neurotoxicity:	0.052	Ototoxicity:	0.812
Hematotoxicity:	0.077	Drug-induced Nephrotoxicity:	0.901
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.079
A549 Cytotoxicity:	0.953	Hek293 Cytotoxicity:	0.265
BCF:	1.016 ? 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:	5.082 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.403 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.441 ? 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
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	seeds	n.a.	n.a.	PMID[11141125]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12398544]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18419154]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19296389]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21910504]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	seeds	n.a.	n.a.	PMID[22011319]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	seed	n.a.	PMID[22011319]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	Barks	n.a.	n.a.	PMID[2348205]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	fruit	n.a.	PMID[8786370]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	bark	n.a.	n.a.	PMID[9214729]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2884	Annona squamosa	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO2884	Annona squamosa	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
IC50	6

Activity Type	# Activity
Cell line	6

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	IC50	=	0.012	ug.mL-1	PMID[22011319]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	0.025	ug.mL-1	PMID[22011319]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	0.052	ug.mL-1	PMID[22011319]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	0.022	ug.mL-1	PMID[22011319]
NPT659	Cell line	SMMC-7721	Homo sapiens	IC50	=	0.057	ug.mL-1	PMID[22011319]
NPT1097	Cell line	MKN-45	Homo sapiens	IC50	=	0.042	ug.mL-1	PMID[22011319]

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 NPC319036 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	16430
0.1-0.2	30035
0.2-0.3	3062
0.3-0.4	96
0.4-0.5	27
0.5-0.6	35
0.6-0.7	55
0.7-0.8	0
0.8-0.85	23
0.85-0.9	11
0.9-0.95	12
0.95-1	10

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473671
1.0	High Similarity	NPC475268
1.0	High Similarity	NPC470400
1.0	High Similarity	NPC77871
1.0	High Similarity	NPC9678
1.0	High Similarity	NPC605867
0.9773	High Similarity	NPC473156
0.9773	High Similarity	NPC282815
0.9773	High Similarity	NPC600956
0.9565	High Similarity	NPC20533
0.9348	High Similarity	NPC132940
0.9333	High Similarity	NPC610454
0.913	High Similarity	NPC604764
0.9091	High Similarity	NPC25764
0.9091	High Similarity	NPC235809
0.9091	High Similarity	NPC39279
0.9091	High Similarity	NPC39167
0.9091	High Similarity	NPC292809
0.9091	High Similarity	NPC202055
0.9091	High Similarity	NPC606804
0.9091	High Similarity	NPC607425
0.9091	High Similarity	NPC608574
0.8913	High Similarity	NPC473649
0.8913	High Similarity	NPC154097
0.8913	High Similarity	NPC159750
0.8913	High Similarity	NPC73248
0.8913	High Similarity	NPC470401
0.8723	High Similarity	NPC219652
0.8723	High Similarity	NPC473840
0.8667	High Similarity	NPC475159
0.8667	High Similarity	NPC131002
0.8667	High Similarity	NPC473780
0.8667	High Similarity	NPC604521
0.84	Intermediate Similarity	NPC120398
0.84	Intermediate Similarity	NPC471567
0.8298	Intermediate Similarity	NPC156804
0.8125	Intermediate Similarity	NPC93794
0.8125	Intermediate Similarity	NPC473504
0.8125	Intermediate Similarity	NPC81778
0.8125	Intermediate Similarity	NPC40066
0.8	Intermediate Similarity	NPC73310
0.8	Intermediate Similarity	NPC473529
0.8	Intermediate Similarity	NPC329838
0.8	Intermediate Similarity	NPC180363
0.8	Intermediate Similarity	NPC94875
0.8	Intermediate Similarity	NPC11332
0.8	Intermediate Similarity	NPC485250
0.8	Intermediate Similarity	NPC145914
0.8	Intermediate Similarity	NPC601174
0.8	Intermediate Similarity	NPC601403
0.8	Intermediate Similarity	NPC603568
0.8	Intermediate Similarity	NPC604330
0.8	Intermediate Similarity	NPC605396
0.8	Intermediate Similarity	NPC608300
0.8	Intermediate Similarity	NPC611200
0.8	Intermediate Similarity	NPC611571
0.7959	Intermediate Similarity	NPC25703
0.7917	Intermediate Similarity	NPC81045
0.7917	Intermediate Similarity	NPC39754
0.7917	Intermediate Similarity	NPC171135
0.7917	Intermediate Similarity	NPC61257
0.7917	Intermediate Similarity	NPC320569
0.7917	Intermediate Similarity	NPC133730
0.7917	Intermediate Similarity	NPC191929
0.7917	Intermediate Similarity	NPC100454
0.7917	Intermediate Similarity	NPC242364
0.7917	Intermediate Similarity	NPC172821
0.7917	Intermediate Similarity	NPC274446
0.7917	Intermediate Similarity	NPC485251
0.7917	Intermediate Similarity	NPC151403
0.7917	Intermediate Similarity	NPC261952
0.7917	Intermediate Similarity	NPC605171
0.7885	Intermediate Similarity	NPC89001
0.7872	Intermediate Similarity	NPC100921
0.7872	Intermediate Similarity	NPC477018
0.78	Intermediate Similarity	NPC42598
0.7755	Intermediate Similarity	NPC163093
0.7755	Intermediate Similarity	NPC600524
0.7755	Intermediate Similarity	NPC608355
0.7692	Intermediate Similarity	NPC258068
0.7692	Intermediate Similarity	NPC473995
0.7692	Intermediate Similarity	NPC476583
0.75	Intermediate Similarity	NPC329829
0.7455	Intermediate Similarity	NPC473905
0.7347	Intermediate Similarity	NPC488253
0.7347	Intermediate Similarity	NPC488251
0.7308	Intermediate Similarity	NPC602738
0.7273	Intermediate Similarity	NPC473520
0.7222	Intermediate Similarity	NPC477014
0.7222	Intermediate Similarity	NPC477013
0.7143	Intermediate Similarity	NPC107986
0.7143	Intermediate Similarity	NPC223871
0.7143	Intermediate Similarity	NPC231009
0.7143	Intermediate Similarity	NPC103284
0.7143	Intermediate Similarity	NPC110710
0.7143	Intermediate Similarity	NPC1083
0.7143	Intermediate Similarity	NPC82795
0.7143	Intermediate Similarity	NPC286338
0.7143	Intermediate Similarity	NPC603931
0.7143	Intermediate Similarity	NPC604237
0.7059	Intermediate Similarity	NPC488632
0.7059	Intermediate Similarity	NPC144415
0.7059	Intermediate Similarity	NPC477011
0.7059	Intermediate Similarity	NPC607439
0.7059	Intermediate Similarity	NPC608157
0.7037	Intermediate Similarity	NPC169511
0.7037	Intermediate Similarity	NPC287164
0.7037	Intermediate Similarity	NPC234077
0.7	Intermediate Similarity	NPC473669
0.6981	Remote Similarity	NPC309211
0.6981	Remote Similarity	NPC477010
0.6939	Remote Similarity	NPC606043
0.6923	Remote Similarity	NPC241360
0.6923	Remote Similarity	NPC293136
0.6863	Remote Similarity	NPC232555
0.6863	Remote Similarity	NPC171174
0.6863	Remote Similarity	NPC114694
0.6863	Remote Similarity	NPC485248
0.6863	Remote Similarity	NPC142117
0.6863	Remote Similarity	NPC480249
0.6863	Remote Similarity	NPC485249
0.6863	Remote Similarity	NPC240695
0.6792	Remote Similarity	NPC178215
0.6792	Remote Similarity	NPC65930
0.6786	Remote Similarity	NPC239517
0.6731	Remote Similarity	NPC134865
0.6731	Remote Similarity	NPC103523
0.6731	Remote Similarity	NPC488627
0.6731	Remote Similarity	NPC488631
0.6667	Remote Similarity	NPC91067
0.6667	Remote Similarity	NPC280612
0.6545	Remote Similarity	NPC69082
0.6545	Remote Similarity	NPC488249
0.6538	Remote Similarity	NPC182383
0.6441	Remote Similarity	NPC473663
0.6441	Remote Similarity	NPC473723
0.6441	Remote Similarity	NPC475173
0.6383	Remote Similarity	NPC609415
0.6364	Remote Similarity	NPC329615
0.6364	Remote Similarity	NPC488250
0.6296	Remote Similarity	NPC280621
0.6296	Remote Similarity	NPC48338
0.6296	Remote Similarity	NPC488628
0.625	Remote Similarity	NPC477012
0.6182	Remote Similarity	NPC473687
0.6182	Remote Similarity	NPC204686
0.6182	Remote Similarity	NPC219498
0.6182	Remote Similarity	NPC308412
0.6182	Remote Similarity	NPC134885
0.6182	Remote Similarity	NPC488247
0.6182	Remote Similarity	NPC210218
0.6182	Remote Similarity	NPC488248
0.6111	Remote Similarity	NPC47937
0.6071	Remote Similarity	NPC20621
0.6071	Remote Similarity	NPC318963
0.6071	Remote Similarity	NPC605101
0.6042	Remote Similarity	NPC608138
0.6034	Remote Similarity	NPC488623
0.6034	Remote Similarity	NPC488624
0.6034	Remote Similarity	NPC480082
0.6034	Remote Similarity	NPC488629
0.6	Remote Similarity	NPC253801
0.6	Remote Similarity	NPC480079
0.6	Remote Similarity	NPC477015
0.5968	Remote Similarity	NPC477017
0.5968	Remote Similarity	NPC477016
0.5965	Remote Similarity	NPC473478
0.5965	Remote Similarity	NPC473651
0.5965	Remote Similarity	NPC66346
0.5862	Remote Similarity	NPC283085
0.5862	Remote Similarity	NPC130359
0.5862	Remote Similarity	NPC14901
0.5789	Remote Similarity	NPC134807
0.5769	Remote Similarity	NPC112685
0.5763	Remote Similarity	NPC320458
0.569	Remote Similarity	NPC473707
0.569	Remote Similarity	NPC20339
0.566	Remote Similarity	NPC480072
0.5593	Remote Similarity	NPC231096
0.5593	Remote Similarity	NPC475581
0.5593	Remote Similarity	NPC62118
0.5593	Remote Similarity	NPC132496
0.5593	Remote Similarity	NPC107717
0.5593	Remote Similarity	NPC488252
0.5574	Remote Similarity	NPC488630
0.5574	Remote Similarity	NPC488625
0.5574	Remote Similarity	NPC322529
0.5574	Remote Similarity	NPC488626
0.55	Remote Similarity	NPC233551
0.55	Remote Similarity	NPC40376
0.55	Remote Similarity	NPC21208
0.5424	Remote Similarity	NPC480076
0.5424	Remote Similarity	NPC480077
0.5333	Remote Similarity	NPC606740
0.5333	Remote Similarity	NPC608614
0.5323	Remote Similarity	NPC480081
0.5227	Remote Similarity	NPC84038
0.5167	Remote Similarity	NPC139418
0.5091	Remote Similarity	NPC228411

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6426
0.1-0.2	2666
0.2-0.3	58
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