NPASS Compound

Natural Product: NPC473840

Natural Product ID	NPC473840
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Spinencin
IUPAC Name	(2S)-4-[(13S)-13-hydroxy-13-[(2S,5S)-5-[(2S,5R)-5-[(1S)-1,5,6-trihydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2H-furan-5-one
Synonyms	spinencin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL453228
PubChem CID	44566508
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 111113 0 0 0 0 0 0 0 0999 V2000 13.9990 0.3274 -0.4396 C 0 0 0 0 0 0 0 0 0 0 0 0 12.5966 0.8878 -0.2832 C 0 0 0 0 0 0 0 0 0 0 0 0 12.0966 1.2058 -1.6699 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7237 1.7687 -1.7009 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6357 0.9344 -1.1312 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5102 -0.3629 -1.8469 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4220 -1.2720 -1.3283 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1004 -0.5509 -1.2384 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0018 -1.4506 -0.7297 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2020 -2.0156 0.6117 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3800 -1.1220 1.7810 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2686 -0.1820 2.1104 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1454 1.0798 1.3482 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7705 1.5745 1.8281 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1756 0.3101 2.4002 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0043 -0.7427 2.1052 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7761 0.1707 1.8820 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0868 -1.1018 2.3009 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0909 -1.1099 1.3161 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4006 -0.2219 0.2178 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7504 0.0550 0.4955 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2981 1.0862 0.1033 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7914 0.9589 -0.2152 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0306 0.2633 -1.4928 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4364 0.0754 -1.8559 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3560 1.1772 -2.1143 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7023 2.1726 -1.0899 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3139 1.5875 0.1676 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6051 0.8513 -0.1477 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1171 0.3175 1.1688 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3930 -0.4400 1.0261 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4535 0.4665 0.4594 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7412 -0.3429 0.3379 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.8540 0.5197 -0.2301 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.1155 -0.2865 -0.3434 C 0 0 0 0 0 0 0 0 0 0 0 0 -14.2714 -0.0734 0.2244 C 0 0 0 0 0 0 0 0 0 0 0 0 -15.2382 -1.1090 -0.1573 C 0 0 1 0 0 0 0 0 0 0 0 0 -14.5448 -1.9598 -1.0095 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.2510 -1.4898 -1.1443 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.3274 -2.0125 -1.8468 O 0 0 0 0 0 0 0 0 0 0 0 0 -15.6493 -1.8169 1.1402 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2749 1.8160 -0.9263 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3665 -2.0490 2.9060 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3766 -2.3787 -2.1413 O 0 0 0 0 0 0 0 0 0 0 0 0 10.6915 -1.1404 -1.7739 O 0 0 0 0 0 0 0 0 0 0 0 0 13.9218 -0.7750 -0.5455 H 0 0 0 0 0 0 0 0 0 0 0 0 14.4697 0.6823 -1.3863 H 0 0 0 0 0 0 0 0 0 0 0 0 14.6292 0.5569 0.4417 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0031 0.1558 0.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7104 1.8393 0.2878 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7810 2.0426 -2.0280 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3123 0.3777 -2.3366 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4700 1.9162 -2.7940 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6983 2.8250 -1.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6747 1.4977 -1.3341 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6696 0.8368 -0.0273 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3198 -0.1232 -2.9322 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7306 -1.5450 -0.2766 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8227 -0.2301 -2.2611 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1958 0.3570 -0.6209 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9210 -2.3334 -1.4453 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0325 -0.9553 -0.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2613 -2.6269 0.8340 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9871 -2.8465 0.6204 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3215 -0.5626 1.8026 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4480 0.1706 3.2286 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9265 1.8264 1.6697 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1005 0.9692 0.2757 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8623 2.3094 2.6372 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1977 1.9849 0.9875 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1088 0.3699 3.5195 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1881 1.0090 2.2714 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6863 -1.0162 3.3336 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7107 -1.9991 2.1434 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2521 -2.1250 0.9041 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0141 -0.7865 1.8006 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4184 -0.7148 -0.7820 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2446 1.7074 1.0083 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1330 2.0040 -0.2701 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3238 0.4890 0.6507 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5065 -0.7443 -1.4091 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4266 0.7758 -2.2924 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9527 -0.6680 -1.1496 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4342 -0.5564 -2.8247 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0411 1.7635 -3.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3539 0.6878 -2.4187 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9692 2.9589 -0.9151 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5767 2.7805 -1.5850 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5816 2.4345 0.8310 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6585 0.8954 0.6872 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3131 1.5075 -0.6681 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3418 -0.0470 -0.7705 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2296 1.1657 1.8871 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2940 -0.3167 1.5970 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6847 -0.8361 2.0226 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2075 -1.2989 0.3171 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5753 1.3260 1.1262 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1977 0.8315 -0.5353 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0020 -0.7027 1.3318 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5957 -1.2059 -0.3397 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5861 0.9256 -1.2249 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0435 1.3579 0.4692 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.4458 0.7744 0.8859 H 0 0 0 0 0 0 0 0 0 0 0 0 -16.1394 -0.6919 -0.6640 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.9040 -2.5758 1.3899 H 0 0 0 0 0 0 0 0 0 0 0 0 -16.6466 -2.3037 1.0021 H 0 0 0 0 0 0 0 0 0 0 0 0 -15.7334 -1.1086 1.9678 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3703 2.5055 -1.2764 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2507 -2.4759 2.9069 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0362 -2.1036 -3.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7374 -1.5402 -0.8718 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 15 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 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 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 22 42 1 0 11 43 1 0 7 44 1 0 6 45 1 0 16 12 1 0 21 17 1 0 39 35 1 0 1 46 1 0 1 47 1 0 1 48 1 0 2 49 1 0 2 50 1 0 3 51 1 0 3 52 1 0 4 53 1 0 4 54 1 0 5 55 1 0 5 56 1 0 6 57 1 0 7 58 1 0 8 59 1 0 8 60 1 0 9 61 1 0 9 62 1 0 10 63 1 0 10 64 1 0 11 65 1 6 12 66 1 1 13 67 1 0 13 68 1 0 14 69 1 0 14 70 1 0 15 71 1 1 17 72 1 6 18 73 1 0 18 74 1 0 19 75 1 0 19 76 1 0 20 77 1 6 22 78 1 1 23 79 1 0 23 80 1 0 24 81 1 0 24 82 1 0 25 83 1 0 25 84 1 0 26 85 1 0 26 86 1 0 27 87 1 0 27 88 1 0 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 45111 1 0 M END

Standard InCHIKey	SWLPIUHJTSWWOJ-UBATVAIOSA-N
Standard InCHI	InChI=1S/C37H66O8/c1-3-4-13-18-29(38)30(39)20-16-21-32(41)34-23-25-36(45-34)35-24-22-33(44-35)31(40)19-15-12-10-8-6-5-7-9-11-14-17-28-26-27(2)43-37(28)42/h26-27,29-36,38-41H,3-25H2,1-2H3/t27-,29?,30?,31-,32-,33-,34+,35-,36-/m0/s1
SMILES	CCCCCC(C(CCC[C@@H]([C@H]1CC[C@H](O1)[C@@H]1CC[C@H](O1)[C@H](CCCCCCCCCCCCC1=C[C@@H](OC1=O)C)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	638.48	Volume:	687.887 ? Van der Waals volume.
Dense:	0.928	LogP:	4.67 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.564 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.134 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	25.0	Rigid Bonds:	16.0
TPSA:	125.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.063	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.942	Fsp³:	0.919
MCE-18:	45.07 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.868	Fluc inhibitor:	0.013 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.105 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.48	Promiscuous compounds:	0.198

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.172	MDCK Permeability:	-4.796
Pgp-inhibitor:	0.022	Pgp-substrate:	0.777
PAMPA:	0.018 ? 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):	0.388
20% Bioavailability (F20%):	0.976	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.898
Plasma Protein Binding (PPB):	96.216%	Volume Distribution (VD):	0.565
Fu:	4.353% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.804
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.686
BSEP inhibitor:	0.881

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.459
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.908
HLM stability:	0.003 ? 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):

5.89

Half-life (T1/2):

1.208

ADMET: Toxicity

hERG Blockers:	0.453	hERG Blockers (10um):	0.877
Human Hepatotoxicity (H-HT):	0.663	Drug-induced Liver Injury (DILI):	0.3
AMES Toxicity:	0.561	Rat Oral Acute Toxicity:	0.278
Maximum Recommended Daily Dose:	0.919	Skin Sensitization:	0.999
Carcinogencity:	0.372	Eye Corrosion:	0.001
Eye Irritation:	0.144	Respiratory Toxicity:	0.804
Drug-induced Neurotoxicity:	0.099	Ototoxicity:	0.906
Hematotoxicity:	0.047	Drug-induced Nephrotoxicity:	0.899
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.955	Hek293 Cytotoxicity:	0.446
BCF:	1.527 ? 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:	5.133 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.319 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.808 ? 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
NPO5133	Annona spinescens	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8699188]
NPO5133	Annona spinescens	Species	Annonaceae	Eukaryota	seeds	n.a.	n.a.	PMID[9461649]
NPO5133	Annona spinescens	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5133	Annona spinescens	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5133	Annona spinescens	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	2

Activity Type	# Activity
Cell line	2

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
NPT91	Cell line	KB	Homo sapiens	ED50	=	1.0	10'-5 ug/ml	PMID[20100877]
NPT189	Cell line	Vero	Chlorocebus aethiops	ED50	=	6.0	10'-3 ug/ml	PMID[20100877]

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 NPC473840 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	16724
0.1-0.2	29856
0.2-0.3	2973
0.3-0.4	77
0.4-0.5	26
0.5-0.6	63
0.6-0.7	44
0.7-0.8	0
0.8-0.85	19
0.85-0.9	14
0.9-0.95	10
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC219652
0.913	High Similarity	NPC25703
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	NPC600524
0.8913	High Similarity	NPC608355
0.875	High Similarity	NPC485250
0.8723	High Similarity	NPC473671
0.8723	High Similarity	NPC475268
0.8723	High Similarity	NPC470400
0.8723	High Similarity	NPC77871
0.8723	High Similarity	NPC9678
0.8723	High Similarity	NPC319036
0.8723	High Similarity	NPC605867
0.8667	High Similarity	NPC329829
0.8511	High Similarity	NPC473156
0.8511	High Similarity	NPC282815
0.8511	High Similarity	NPC600956
0.8462	Intermediate Similarity	NPC473905
0.8367	Intermediate Similarity	NPC20533
0.8163	Intermediate Similarity	NPC132940
0.8125	Intermediate Similarity	NPC610454
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	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	NPC604764
0.78	Intermediate Similarity	NPC65930
0.7755	Intermediate Similarity	NPC473649
0.7755	Intermediate Similarity	NPC154097
0.7755	Intermediate Similarity	NPC159750
0.7755	Intermediate Similarity	NPC73248
0.7755	Intermediate Similarity	NPC470401
0.7692	Intermediate Similarity	NPC120398
0.7692	Intermediate Similarity	NPC473995
0.7692	Intermediate Similarity	NPC471567
0.75	Intermediate Similarity	NPC475159
0.75	Intermediate Similarity	NPC131002
0.75	Intermediate Similarity	NPC473780
0.75	Intermediate Similarity	NPC604521
0.75	Intermediate Similarity	NPC609415
0.7308	Intermediate Similarity	NPC329615
0.7273	Intermediate Similarity	NPC473520
0.72	Intermediate Similarity	NPC81045
0.72	Intermediate Similarity	NPC39754
0.72	Intermediate Similarity	NPC171135
0.72	Intermediate Similarity	NPC61257
0.72	Intermediate Similarity	NPC320569
0.72	Intermediate Similarity	NPC133730
0.72	Intermediate Similarity	NPC191929
0.72	Intermediate Similarity	NPC100454
0.72	Intermediate Similarity	NPC242364
0.72	Intermediate Similarity	NPC172821
0.72	Intermediate Similarity	NPC156804
0.72	Intermediate Similarity	NPC274446
0.72	Intermediate Similarity	NPC485251
0.72	Intermediate Similarity	NPC151403
0.72	Intermediate Similarity	NPC261952
0.72	Intermediate Similarity	NPC605171
0.717	Intermediate Similarity	NPC477012
0.7059	Intermediate Similarity	NPC93794
0.7059	Intermediate Similarity	NPC134865
0.7059	Intermediate Similarity	NPC473504
0.7059	Intermediate Similarity	NPC163093
0.7059	Intermediate Similarity	NPC103523
0.7059	Intermediate Similarity	NPC144415
0.7059	Intermediate Similarity	NPC81778
0.7059	Intermediate Similarity	NPC40066
0.7059	Intermediate Similarity	NPC488627
0.7059	Intermediate Similarity	NPC488631
0.7059	Intermediate Similarity	NPC477011
0.7059	Intermediate Similarity	NPC607439
0.7059	Intermediate Similarity	NPC608157
0.6964	Remote Similarity	NPC91067
0.6923	Remote Similarity	NPC241360
0.6923	Remote Similarity	NPC293136
0.6909	Remote Similarity	NPC89001
0.6909	Remote Similarity	NPC480082
0.6842	Remote Similarity	NPC253801
0.68	Remote Similarity	NPC100921
0.68	Remote Similarity	NPC477018
0.6792	Remote Similarity	NPC42598
0.6727	Remote Similarity	NPC258068
0.6727	Remote Similarity	NPC476583
0.6667	Remote Similarity	NPC602738
0.6429	Remote Similarity	NPC169511
0.6429	Remote Similarity	NPC287164
0.6429	Remote Similarity	NPC234077
0.6346	Remote Similarity	NPC488253
0.6346	Remote Similarity	NPC488251
0.6316	Remote Similarity	NPC320458
0.6316	Remote Similarity	NPC477014
0.6316	Remote Similarity	NPC477013
0.6275	Remote Similarity	NPC606043
0.625	Remote Similarity	NPC473478
0.625	Remote Similarity	NPC473651
0.625	Remote Similarity	NPC66346
0.6207	Remote Similarity	NPC239517
0.6154	Remote Similarity	NPC107986
0.6154	Remote Similarity	NPC223871
0.6154	Remote Similarity	NPC231009
0.6154	Remote Similarity	NPC103284
0.6154	Remote Similarity	NPC110710
0.6154	Remote Similarity	NPC1083
0.6154	Remote Similarity	NPC82795
0.6154	Remote Similarity	NPC286338
0.6154	Remote Similarity	NPC603931
0.6154	Remote Similarity	NPC604237
0.614	Remote Similarity	NPC283085
0.614	Remote Similarity	NPC132496
0.6111	Remote Similarity	NPC488632
0.6102	Remote Similarity	NPC322529
0.6071	Remote Similarity	NPC309211
0.6071	Remote Similarity	NPC477010
0.6038	Remote Similarity	NPC473669
0.6	Remote Similarity	NPC480079
0.6	Remote Similarity	NPC477015
0.5926	Remote Similarity	NPC232555
0.5926	Remote Similarity	NPC171174
0.5926	Remote Similarity	NPC114694
0.5926	Remote Similarity	NPC485248
0.5926	Remote Similarity	NPC142117
0.5926	Remote Similarity	NPC480249
0.5926	Remote Similarity	NPC485249
0.5926	Remote Similarity	NPC240695
0.5902	Remote Similarity	NPC473663
0.5902	Remote Similarity	NPC473723
0.5902	Remote Similarity	NPC475173
0.5893	Remote Similarity	NPC178215
0.5862	Remote Similarity	NPC231096
0.5862	Remote Similarity	NPC475581
0.5862	Remote Similarity	NPC62118
0.5862	Remote Similarity	NPC107717
0.5862	Remote Similarity	NPC488252
0.5862	Remote Similarity	NPC606740
0.5862	Remote Similarity	NPC608614
0.5833	Remote Similarity	NPC280612
0.5789	Remote Similarity	NPC600188
0.5763	Remote Similarity	NPC233551
0.5763	Remote Similarity	NPC40376
0.5763	Remote Similarity	NPC21208
0.5714	Remote Similarity	NPC280621
0.5714	Remote Similarity	NPC48338
0.5714	Remote Similarity	NPC488628
0.569	Remote Similarity	NPC69082
0.569	Remote Similarity	NPC488249
0.5636	Remote Similarity	NPC182383
0.5614	Remote Similarity	NPC473687
0.5614	Remote Similarity	NPC204686
0.5614	Remote Similarity	NPC219498
0.5614	Remote Similarity	NPC308412
0.5614	Remote Similarity	NPC134885
0.5614	Remote Similarity	NPC488247
0.5614	Remote Similarity	NPC210218
0.5614	Remote Similarity	NPC488248
0.5574	Remote Similarity	NPC480081
0.5517	Remote Similarity	NPC20621
0.5517	Remote Similarity	NPC318963
0.5517	Remote Similarity	NPC134807
0.5517	Remote Similarity	NPC488250
0.5517	Remote Similarity	NPC605101
0.55	Remote Similarity	NPC488623
0.55	Remote Similarity	NPC488624
0.55	Remote Similarity	NPC488629
0.5333	Remote Similarity	NPC130359
0.5333	Remote Similarity	NPC14901
0.5263	Remote Similarity	NPC47937
0.5231	Remote Similarity	NPC279267
0.5231	Remote Similarity	NPC477017
0.5231	Remote Similarity	NPC477016
0.5227	Remote Similarity	NPC84038
0.5185	Remote Similarity	NPC112685
0.5098	Remote Similarity	NPC608138
0.5091	Remote Similarity	NPC228411
0.5091	Remote Similarity	NPC480072
0.5085	Remote Similarity	NPC478998
0.5085	Remote Similarity	NPC473904
0.5079	Remote Similarity	NPC488630
0.5079	Remote Similarity	NPC488625
0.5079	Remote Similarity	NPC488626

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473840 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6449
0.1-0.2	2641
0.2-0.3	60
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