NPASS Compound

Natural Product: NPC133730

Natural Product ID	NPC133730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-4-[(2R,9R)-2,9-Dihydroxy-9-[(2R,5R)-5-[(2R,5R)-5-[(1R)-1-Hydroxytridecyl]Oxolan-2-Yl]Oxolan-2-Yl]Nonyl]-2-Methyl-2H-Furan-5-One
IUPAC Name	(2S)-4-[(2R,9R)-2,9-dihydroxy-9-[(2R,5R)-5-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]oxolan-2-yl]nonyl]-2-methyl-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL266014
PubChem CID	10031413
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 104106 0 0 0 0 0 0 0 0999 V2000 -12.2554 1.0885 -1.0506 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4821 1.0004 0.2483 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7153 -0.2367 1.0214 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4681 -1.5526 0.4258 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1319 -1.9474 -0.0463 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5154 -1.1912 -1.1619 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1662 -1.8051 -1.5324 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1893 -1.7357 -0.3917 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8568 -2.3408 -0.8078 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8180 -2.2836 0.2805 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5368 -0.8425 0.6825 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5018 -0.7197 1.7447 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2716 0.7069 2.1481 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8072 1.5151 0.9894 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7337 3.0121 1.3368 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7728 3.4243 0.1993 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7785 2.2860 0.3745 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5871 1.1850 0.4642 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2597 2.2256 -0.6821 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0537 3.4723 -0.8597 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4809 2.9889 -0.5306 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1549 1.7587 0.2499 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1439 1.1651 -0.4581 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2704 0.9198 0.7087 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8613 -0.0875 -0.1868 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4445 0.4206 -1.4622 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0840 -0.6890 -2.2825 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2021 -1.3782 -1.5251 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2740 -0.3856 -1.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4219 -0.9882 -0.3942 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0899 -2.0499 -1.2337 C 0 0 2 0 0 0 0 0 0 0 0 0 10.2192 -2.6249 -0.4377 C 0 0 0 0 0 0 0 0 0 0 0 0 11.2481 -1.6527 -0.0314 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6171 -1.3213 1.2132 C 0 0 0 0 0 0 0 0 0 0 0 0 12.6849 -0.3071 1.1945 C 0 0 1 0 0 0 0 0 0 0 0 0 12.9493 -0.0525 -0.1460 O 0 0 0 0 0 0 0 0 0 0 0 0 12.0847 -0.8573 -0.8990 C 0 0 0 0 0 0 0 0 0 0 0 0 12.0466 -0.8804 -2.1672 O 0 0 0 0 0 0 0 0 0 0 0 0 12.2007 0.9064 1.9617 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5599 -1.4946 -2.4040 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2341 1.7214 1.3733 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3474 0.8179 3.1898 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.2549 2.1558 -1.3550 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2981 0.7728 -0.8519 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.7893 0.5142 -1.8661 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4614 1.3290 0.1688 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0108 1.8251 0.8897 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.7602 -0.2382 1.4861 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0470 -0.1539 1.9467 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.7600 -2.3237 1.2224 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2237 -1.8043 -0.3889 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4497 -1.9855 0.8574 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1906 -3.0364 -0.3568 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2559 -0.1356 -0.9186 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1331 -1.2122 -2.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8029 -1.2505 -2.4228 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3372 -2.8788 -1.7598 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0233 -0.6416 -0.1668 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5636 -2.1941 0.5240 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0172 -3.3894 -1.0824 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4800 -1.7949 -1.6976 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9357 -2.8361 -0.0468 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2315 -2.8522 1.1585 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2855 -0.2774 -0.2367 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4968 -0.4446 1.1063 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5515 -1.1665 1.3284 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7765 -1.3066 2.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2674 1.1251 2.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6201 1.4921 0.2029 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6967 3.5081 1.2555 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1837 3.1606 2.2826 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3657 3.3214 -0.7230 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3399 4.4038 0.3847 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3563 2.4488 1.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2716 2.0237 -1.6515 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8324 4.2707 -0.1353 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9965 3.8635 -1.9044 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9652 2.8600 -1.4927 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9994 3.7351 0.1197 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6199 2.1716 1.1916 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8414 0.3168 1.6007 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7017 -0.6493 0.3270 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1135 -0.9139 -0.3828 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0965 1.2779 -1.3834 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5538 0.7284 -2.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3288 -1.4430 -2.5428 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5415 -0.2114 -3.1729 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6591 -2.0809 -2.2824 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8638 -1.9871 -0.6877 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6245 0.1230 -2.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7691 0.4136 -0.5462 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0576 -1.4042 0.5705 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1348 -0.1862 -0.1337 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3633 -2.8428 -1.5338 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7031 -3.4582 -1.0181 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8483 -3.1292 0.4918 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1590 -1.7696 2.0798 H 0 0 0 0 0 0 0 0 0 0 0 0 13.6210 -0.6695 1.6721 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5220 1.4731 1.2971 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5825 0.5728 2.8378 H 0 0 0 0 0 0 0 0 0 0 0 0 13.0239 1.5196 2.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0099 -1.6990 -3.2016 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0337 1.8500 0.8096 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9792 -0.0800 3.4391 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 22 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 2 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 2 0 35 39 1 0 31 40 1 0 24 41 1 0 13 42 1 0 18 14 1 0 23 19 1 0 37 33 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 1 14 69 1 6 15 70 1 0 15 71 1 0 16 72 1 0 16 73 1 0 17 74 1 1 19 75 1 6 20 76 1 0 20 77 1 0 21 78 1 0 21 79 1 0 22 80 1 1 24 81 1 1 25 82 1 0 25 83 1 0 26 84 1 0 26 85 1 0 27 86 1 0 27 87 1 0 28 88 1 0 28 89 1 0 29 90 1 0 29 91 1 0 30 92 1 0 30 93 1 0 31 94 1 6 32 95 1 0 32 96 1 0 34 97 1 0 35 98 1 1 39 99 1 0 39100 1 0 39101 1 0 40102 1 0 41103 1 0 42104 1 0 M END

Standard InCHIKey	CKZPVMXHDAMANG-GHRGOOLJSA-N
Standard InCHI	InChI=1S/C35H62O7/c1-3-4-5-6-7-8-9-10-11-15-18-29(37)31-20-22-33(41-31)34-23-21-32(42-34)30(38)19-16-13-12-14-17-28(36)25-27-24-26(2)40-35(27)39/h24,26,28-34,36-38H,3-23,25H2,1-2H3/t26-,28+,29+,30+,31+,32+,33+,34+/m0/s1
SMILES	CCCCCCCCCCCC[C@H]([C@H]1CC[C@@H](O1)[C@H]1CC[C@@H](O1)[C@@H](CCCCCC[C@H](CC1=C[C@@H](OC1=O)C)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	594.45	Volume:	644.505 ? Van der Waals volume.
Dense:	0.922	LogP:	5.178 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.77 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.07 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	23.0	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:	0.086	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.741	Fsp³:	0.914
MCE-18:	43.104 ? 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:	0.887	Fluc inhibitor:	0.029 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.059 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.587	Promiscuous compounds:	0.326

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.138	MDCK Permeability:	-4.846
Pgp-inhibitor:	0.005	Pgp-substrate:	0.906
PAMPA:	0.095 ? 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):	0.004
20% Bioavailability (F20%):	0.954	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.952
Plasma Protein Binding (PPB):	97.083%	Volume Distribution (VD):	0.622
Fu:	3.555% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.858
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.669
BSEP inhibitor:	0.973

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.871	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.231
CYP3A4-inhibitor:	0.061	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.97
HLM stability:	0.002 ? 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):

5.753

Half-life (T1/2):

1.109

ADMET: Toxicity

hERG Blockers:	0.504	hERG Blockers (10um):	0.768
Human Hepatotoxicity (H-HT):	0.648	Drug-induced Liver Injury (DILI):	0.45
AMES Toxicity:	0.542	Rat Oral Acute Toxicity:	0.18
Maximum Recommended Daily Dose:	0.868	Skin Sensitization:	1.0
Carcinogencity:	0.567	Eye Corrosion:	0.013
Eye Irritation:	0.713	Respiratory Toxicity:	0.899
Drug-induced Neurotoxicity:	0.127	Ototoxicity:	0.592
Hematotoxicity:	0.144	Drug-induced Nephrotoxicity:	0.814
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.981	Hek293 Cytotoxicity:	0.444
BCF:	1.353 ? 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:	4.975 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.06 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.165 ? 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
NPO6886	Asimina longifolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7494147]
NPO6886	Asimina longifolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8627602]
NPO6886	Asimina longifolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6886	Asimina longifolia	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	1
ED50	6

Activity Type	# Activity
Cell line	7

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	IC50	>	1000.0	ug.mL-1	DrugMatrix in vitro pharmacology data
NPT81	Cell line	A549	Homo sapiens	ED50	=	0.143	ug ml-1	DrugMatrix in vivo data: Hematology
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	0.0154	ug ml-1	DrugMatrix in vivo data: Hematology
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	0.00332	ug ml-1	DrugMatrix in vivo data: Hematology
NPT376	Cell line	A498	Homo sapiens	ED50	=	0.064	ug ml-1	DrugMatrix in vivo data: Hematology
NPT306	Cell line	PC-3	Homo sapiens	ED50	=	2.2	ug ml-1	DrugMatrix in vivo data: Hematology
NPT783	Cell line	MIA PaCa-2	Homo sapiens	ED50	=	0.0792	ug ml-1	DOI[10.1007/s00044-011-9876-x]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference
-	Artemia	LC50	=	7.34	ug.mL-1	DrugMatrix in vivo data: Hematology

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 NPC133730 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	16229
0.1-0.2	30285
0.2-0.3	3006
0.3-0.4	102
0.4-0.5	29
0.5-0.6	18
0.6-0.7	51
0.7-0.8	0
0.8-0.85	27
0.85-0.9	14
0.9-0.95	2
0.95-1	18

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC81045
1.0	High Similarity	NPC39754
1.0	High Similarity	NPC171135
1.0	High Similarity	NPC61257
1.0	High Similarity	NPC320569
1.0	High Similarity	NPC191929
1.0	High Similarity	NPC100454
1.0	High Similarity	NPC242364
1.0	High Similarity	NPC172821
1.0	High Similarity	NPC274446
1.0	High Similarity	NPC485251
1.0	High Similarity	NPC151403
1.0	High Similarity	NPC261952
1.0	High Similarity	NPC605171
0.9767	High Similarity	NPC93794
0.9767	High Similarity	NPC473504
0.9767	High Similarity	NPC81778
0.9767	High Similarity	NPC40066
0.9333	High Similarity	NPC42598
0.913	High Similarity	NPC602738
0.8837	High Similarity	NPC606043
0.875	High Similarity	NPC169511
0.875	High Similarity	NPC287164
0.875	High Similarity	NPC234077
0.8636	High Similarity	NPC107986
0.8636	High Similarity	NPC223871
0.8636	High Similarity	NPC231009
0.8636	High Similarity	NPC103284
0.8636	High Similarity	NPC110710
0.8636	High Similarity	NPC1083
0.8636	High Similarity	NPC82795
0.8636	High Similarity	NPC286338
0.8636	High Similarity	NPC603931
0.8636	High Similarity	NPC604237
0.8444	Intermediate Similarity	NPC488253
0.8444	Intermediate Similarity	NPC473669
0.8444	Intermediate Similarity	NPC488251
0.84	Intermediate Similarity	NPC239517
0.8261	Intermediate Similarity	NPC232555
0.8261	Intermediate Similarity	NPC171174
0.8261	Intermediate Similarity	NPC114694
0.8261	Intermediate Similarity	NPC485248
0.8261	Intermediate Similarity	NPC142117
0.8261	Intermediate Similarity	NPC480249
0.8261	Intermediate Similarity	NPC485249
0.8261	Intermediate Similarity	NPC240695
0.8235	Intermediate Similarity	NPC91067
0.8085	Intermediate Similarity	NPC488632
0.8085	Intermediate Similarity	NPC473649
0.8085	Intermediate Similarity	NPC473156
0.8085	Intermediate Similarity	NPC134865
0.8085	Intermediate Similarity	NPC154097
0.8085	Intermediate Similarity	NPC103523
0.8085	Intermediate Similarity	NPC159750
0.8085	Intermediate Similarity	NPC73248
0.8085	Intermediate Similarity	NPC282815
0.8085	Intermediate Similarity	NPC488627
0.8085	Intermediate Similarity	NPC488631
0.8085	Intermediate Similarity	NPC470401
0.8085	Intermediate Similarity	NPC600956
0.8085	Intermediate Similarity	NPC610454
0.7925	Intermediate Similarity	NPC473663
0.7925	Intermediate Similarity	NPC473723
0.7925	Intermediate Similarity	NPC475173
0.7917	Intermediate Similarity	NPC280621
0.7917	Intermediate Similarity	NPC473671
0.7917	Intermediate Similarity	NPC475268
0.7917	Intermediate Similarity	NPC470400
0.7917	Intermediate Similarity	NPC77871
0.7917	Intermediate Similarity	NPC48338
0.7917	Intermediate Similarity	NPC9678
0.7917	Intermediate Similarity	NPC319036
0.7917	Intermediate Similarity	NPC488628
0.7917	Intermediate Similarity	NPC604764
0.7917	Intermediate Similarity	NPC605867
0.7872	Intermediate Similarity	NPC182383
0.7826	Intermediate Similarity	NPC25764
0.7826	Intermediate Similarity	NPC235809
0.7826	Intermediate Similarity	NPC39279
0.7826	Intermediate Similarity	NPC39167
0.7826	Intermediate Similarity	NPC292809
0.7826	Intermediate Similarity	NPC202055
0.7826	Intermediate Similarity	NPC606804
0.7826	Intermediate Similarity	NPC607425
0.7826	Intermediate Similarity	NPC608574
0.7755	Intermediate Similarity	NPC178215
0.7755	Intermediate Similarity	NPC473687
0.7755	Intermediate Similarity	NPC204686
0.7755	Intermediate Similarity	NPC219498
0.7755	Intermediate Similarity	NPC308412
0.7755	Intermediate Similarity	NPC134885
0.7755	Intermediate Similarity	NPC488247
0.7755	Intermediate Similarity	NPC132940
0.7755	Intermediate Similarity	NPC210218
0.7755	Intermediate Similarity	NPC488248
0.76	Intermediate Similarity	NPC20621
0.76	Intermediate Similarity	NPC318963
0.76	Intermediate Similarity	NPC20533
0.76	Intermediate Similarity	NPC488250
0.76	Intermediate Similarity	NPC605101
0.75	Intermediate Similarity	NPC488623
0.75	Intermediate Similarity	NPC488624
0.75	Intermediate Similarity	NPC488629
0.7451	Intermediate Similarity	NPC473478
0.7451	Intermediate Similarity	NPC69082
0.7451	Intermediate Similarity	NPC473651
0.7451	Intermediate Similarity	NPC488249
0.7451	Intermediate Similarity	NPC66346
0.7442	Intermediate Similarity	NPC608138
0.7391	Intermediate Similarity	NPC112685
0.7347	Intermediate Similarity	NPC47937
0.7347	Intermediate Similarity	NPC477011
0.7347	Intermediate Similarity	NPC600524
0.7347	Intermediate Similarity	NPC608355
0.7308	Intermediate Similarity	NPC120398
0.7308	Intermediate Similarity	NPC283085
0.7308	Intermediate Similarity	NPC130359
0.7308	Intermediate Similarity	NPC14901
0.7308	Intermediate Similarity	NPC471567
0.7255	Intermediate Similarity	NPC134807
0.72	Intermediate Similarity	NPC219652
0.72	Intermediate Similarity	NPC473840
0.72	Intermediate Similarity	NPC480079
0.717	Intermediate Similarity	NPC89001
0.7083	Intermediate Similarity	NPC100921
0.7083	Intermediate Similarity	NPC475159
0.7083	Intermediate Similarity	NPC131002
0.7083	Intermediate Similarity	NPC473780
0.7083	Intermediate Similarity	NPC477018
0.7083	Intermediate Similarity	NPC604521
0.6981	Remote Similarity	NPC231096
0.6981	Remote Similarity	NPC475581
0.6981	Remote Similarity	NPC62118
0.6981	Remote Similarity	NPC132496
0.6981	Remote Similarity	NPC107717
0.6981	Remote Similarity	NPC488252
0.6923	Remote Similarity	NPC485250
0.6923	Remote Similarity	NPC605396
0.6909	Remote Similarity	NPC488630
0.6909	Remote Similarity	NPC488625
0.6909	Remote Similarity	NPC488626
0.6863	Remote Similarity	NPC25703
0.6852	Remote Similarity	NPC233551
0.6852	Remote Similarity	NPC40376
0.6852	Remote Similarity	NPC21208
0.6809	Remote Similarity	NPC73310
0.6809	Remote Similarity	NPC473529
0.6809	Remote Similarity	NPC180363
0.6809	Remote Similarity	NPC94875
0.6809	Remote Similarity	NPC11332
0.6809	Remote Similarity	NPC145914
0.6809	Remote Similarity	NPC601174
0.6809	Remote Similarity	NPC601403
0.6809	Remote Similarity	NPC603568
0.6809	Remote Similarity	NPC604330
0.6809	Remote Similarity	NPC608300
0.6809	Remote Similarity	NPC611200
0.6809	Remote Similarity	NPC611571
0.68	Remote Similarity	NPC156804
0.6792	Remote Similarity	NPC473707
0.6792	Remote Similarity	NPC20339
0.6667	Remote Similarity	NPC163093
0.6667	Remote Similarity	NPC473995
0.6667	Remote Similarity	NPC606740
0.6667	Remote Similarity	NPC608614
0.6607	Remote Similarity	NPC480081
0.64	Remote Similarity	NPC329829
0.6316	Remote Similarity	NPC473520
0.6296	Remote Similarity	NPC309211
0.6296	Remote Similarity	NPC329838
0.6296	Remote Similarity	NPC477010
0.6207	Remote Similarity	NPC473905
0.6167	Remote Similarity	NPC482766
0.6167	Remote Similarity	NPC279267
0.6071	Remote Similarity	NPC258068
0.6071	Remote Similarity	NPC476583
0.6038	Remote Similarity	NPC488246
0.6038	Remote Similarity	NPC144415
0.6038	Remote Similarity	NPC480080
0.6038	Remote Similarity	NPC607439
0.6038	Remote Similarity	NPC608157
0.5965	Remote Similarity	NPC477014
0.5965	Remote Similarity	NPC477013
0.5926	Remote Similarity	NPC241360
0.5926	Remote Similarity	NPC293136
0.5882	Remote Similarity	NPC480072
0.5818	Remote Similarity	NPC473904
0.5818	Remote Similarity	NPC65930
0.5614	Remote Similarity	NPC11456
0.5614	Remote Similarity	NPC480076
0.5614	Remote Similarity	NPC480077
0.5614	Remote Similarity	NPC477012
0.5517	Remote Similarity	NPC488244
0.55	Remote Similarity	NPC280612
0.5455	Remote Similarity	NPC480078
0.5455	Remote Similarity	NPC480071
0.5439	Remote Similarity	NPC329615
0.5439	Remote Similarity	NPC480075
0.5397	Remote Similarity	NPC477017

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC133730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6294
0.1-0.2	2797
0.2-0.3	59
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