NPASS Compound

Natural Product: NPC309211

Natural Product ID	NPC309211
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Calamistrin E
IUPAC Name	(2S)-4-[(3R,13R)-3,13-dihydroxy-13-[(2R,5R)-5-[(Z,1R)-1-hydroxytetradec-4-enyl]oxolan-2-yl]tridecyl]-2-methyl-2H-furan-5-one
Synonyms	Calamistrin E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL451654
PubChem CID	11801608
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 106107 0 0 0 0 0 0 0 0999 V2000 -12.8741 2.0599 2.9812 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4787 1.4636 3.0996 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.5878 -0.0283 3.1804 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.2384 -0.6201 1.9795 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4507 -0.3292 0.7220 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0729 -0.8977 0.7812 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2443 -0.6592 -0.4684 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0272 0.7965 -0.7733 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2709 1.5681 0.2243 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8790 1.4484 0.5141 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9324 0.8051 -0.0661 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9514 -0.0198 -1.2341 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0190 0.4644 -2.3516 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5959 0.5427 -1.9999 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9155 -0.7034 -1.5528 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1054 -1.9108 -2.3763 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6602 -2.2637 -2.7594 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0340 -0.8958 -2.6393 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4802 -0.9585 -2.6713 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9614 0.4625 -2.6621 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4240 0.6739 -2.7069 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2124 0.1041 -1.5724 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6954 0.4024 -1.7342 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4534 -0.1609 -0.5256 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2874 -1.6308 -0.3727 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9539 -2.2919 0.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3982 -2.3764 0.9233 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2485 -1.1717 1.0365 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7189 -1.6123 1.3124 C 0 0 2 0 0 0 0 0 0 0 0 0 10.5264 -0.3473 1.4065 C 0 0 0 0 0 0 0 0 0 0 0 0 11.9745 -0.6389 1.6776 C 0 0 0 0 0 0 0 0 0 0 0 0 12.7528 0.6172 1.7550 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2640 1.8325 1.6092 C 0 0 0 0 0 0 0 0 0 0 0 0 13.3714 2.8147 1.7585 C 0 0 2 0 0 0 0 0 0 0 0 0 13.5225 3.5911 0.4618 C 0 0 0 0 0 0 0 0 0 0 0 0 14.5242 2.0360 1.9961 O 0 0 0 0 0 0 0 0 0 0 0 0 14.2031 0.6931 2.0062 C 0 0 0 0 0 0 0 0 0 0 0 0 14.9655 -0.2884 2.1890 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1178 -2.4340 0.2816 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9856 -1.7644 -1.6883 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5467 -0.4244 -1.4590 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3803 1.5444 -1.0681 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.1549 1.9793 1.9064 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.5563 1.4359 3.6228 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.8284 3.0864 3.3554 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8833 1.8289 2.2541 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9612 1.7998 4.0281 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5932 -0.4532 3.4026 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2244 -0.2729 4.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.4431 -1.6972 2.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2280 -0.0998 1.8496 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.4482 0.7669 0.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9883 -0.8395 -0.1044 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0967 -2.0208 0.8919 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5308 -0.5149 1.6522 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7200 -1.1636 -1.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3094 -1.2154 -0.2860 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1146 1.2098 -0.8209 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7321 0.9835 -1.8502 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5850 2.6845 0.1686 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8103 1.3249 1.2307 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5481 2.0605 1.4692 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9269 0.9199 0.4680 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8675 -0.2860 -1.7318 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4834 -1.0288 -0.9626 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2417 -0.1891 -3.2346 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3400 1.4845 -2.6861 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0586 0.9069 -2.9283 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2085 -0.9747 -0.4926 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6613 -1.8123 -3.2981 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5571 -2.7717 -1.8075 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6270 -2.6750 -3.7817 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2792 -2.9668 -1.9916 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3382 -0.3067 -3.5262 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7456 -1.3859 -3.6647 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5277 1.0382 -3.5388 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5292 1.0212 -1.7780 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8048 0.2754 -3.6880 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6001 1.7829 -2.7240 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1023 -1.0168 -1.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8968 0.4347 -0.5853 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8219 1.4802 -1.8172 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0852 -0.0768 -2.6432 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0625 0.3212 0.4109 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4921 0.1346 -0.6948 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1656 -1.7901 -0.2122 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5063 -2.1571 -1.3568 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5671 -3.3850 0.8004 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4602 -1.8577 1.7100 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5820 -3.0279 1.8557 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8016 -3.0764 0.1161 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9914 -0.4721 1.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3271 -0.6090 0.0789 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6994 -2.1641 2.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4790 0.1544 0.3980 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1084 0.2958 2.1940 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3920 -1.3061 0.9133 H 0 0 0 0 0 0 0 0 0 0 0 0 12.0431 -1.1808 2.6628 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2472 2.1124 1.4141 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1803 3.5236 2.5936 H 0 0 0 0 0 0 0 0 0 0 0 0 14.1086 3.0124 -0.2874 H 0 0 0 0 0 0 0 0 0 0 0 0 14.0326 4.5614 0.6176 H 0 0 0 0 0 0 0 0 0 0 0 0 12.5171 3.8125 0.0221 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6765 -2.1150 -0.5539 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8203 -1.4075 -0.7800 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8052 2.3915 -1.2911 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 2 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 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 2 0 33 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 37 38 2 0 29 39 1 0 19 40 1 0 18 41 1 0 14 42 1 0 41 15 1 0 37 32 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 11 63 1 0 12 64 1 0 12 65 1 0 13 66 1 0 13 67 1 0 14 68 1 6 15 69 1 1 16 70 1 0 16 71 1 0 17 72 1 0 17 73 1 0 18 74 1 6 19 75 1 6 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 1 30 95 1 0 30 96 1 0 31 97 1 0 31 98 1 0 33 99 1 0 34100 1 1 35101 1 0 35102 1 0 35103 1 0 39104 1 0 40105 1 0 42106 1 0 M END

Standard InCHIKey	UNXIMIFMCNSOAC-QBXDJIRYSA-N
Standard InCHI	InChI=1S/C36H64O6/c1-3-4-5-6-7-8-9-10-13-16-19-22-32(38)34-26-27-35(42-34)33(39)23-20-17-14-11-12-15-18-21-31(37)25-24-30-28-29(2)41-36(30)40/h13,16,28-29,31-35,37-39H,3-12,14-15,17-27H2,1-2H3/b16-13-/t29-,31+,32+,33+,34+,35+/m0/s1
SMILES	CCCCCCCCC/C=CCC[C@H]([C@H]1CC[C@H]([C@@H](CCCCCCCCC[C@H](CCC2=C[C@H](C)OC2=O)O)O)O1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.47	Volume:	658.931 ? Van der Waals volume.
Dense:	0.899	LogP:	6.479 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.426 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.685 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	12.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.053	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.578	Fsp³:	0.861
MCE-18:	30.09 ? 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:	0.767	Fluc inhibitor:	0.123 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.053 ? 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:	0.6	Promiscuous compounds:	0.245

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.099	MDCK Permeability:	-4.78
Pgp-inhibitor:	0.058	Pgp-substrate:	0.059
PAMPA:	0.013 ? 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):	0.1
20% Bioavailability (F20%):	0.989	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.9
Plasma Protein Binding (PPB):	97.26%	Volume Distribution (VD):	0.062
Fu:	1.595% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.769
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.585
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.957
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.968	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.042	CYP2D6-substrate:	0.992
CYP3A4-inhibitor:	0.012	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.009 ? 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):

5.924

Half-life (T1/2):

0.953

ADMET: Toxicity

hERG Blockers:	0.44	hERG Blockers (10um):	0.823
Human Hepatotoxicity (H-HT):	0.588	Drug-induced Liver Injury (DILI):	0.035
AMES Toxicity:	0.307	Rat Oral Acute Toxicity:	0.103
Maximum Recommended Daily Dose:	0.929	Skin Sensitization:	1.0
Carcinogencity:	0.397	Eye Corrosion:	0.046
Eye Irritation:	0.754	Respiratory Toxicity:	0.923
Drug-induced Neurotoxicity:	0.059	Ototoxicity:	0.637
Hematotoxicity:	0.038	Drug-induced Nephrotoxicity:	0.954
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.964	Hek293 Cytotoxicity:	0.338
BCF:	1.121 ? 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:	5.077 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.377 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.199 ? 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
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075755]
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11000019]
NPO210	Uvaria calamistrata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO210	Uvaria calamistrata	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	3

Activity Type	# Activity
Cell line	2
Non-molecular	1

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	0.0273	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT91	Cell line	KB	Homo sapiens	IC50	=	0.375	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	0.00397	ug.mL-1	PMID[11000019]

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 NPC309211 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	17324
0.1-0.2	28985
0.2-0.3	3090
0.3-0.4	221
0.4-0.5	38
0.5-0.6	54
0.6-0.7	94
0.7-0.8	0
0.8-0.85	3
0.85-0.9	3
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8696	High Similarity	NPC100921
0.8696	High Similarity	NPC477018
0.8542	High Similarity	NPC607439
0.84	Intermediate Similarity	NPC488250
0.8235	Intermediate Similarity	NPC69082
0.8235	Intermediate Similarity	NPC488249
0.7917	Intermediate Similarity	NPC475159
0.7917	Intermediate Similarity	NPC131002
0.7917	Intermediate Similarity	NPC473780
0.7917	Intermediate Similarity	NPC604521
0.78	Intermediate Similarity	NPC473649
0.78	Intermediate Similarity	NPC154097
0.78	Intermediate Similarity	NPC159750
0.78	Intermediate Similarity	NPC73248
0.78	Intermediate Similarity	NPC470401
0.7692	Intermediate Similarity	NPC477010
0.7647	Intermediate Similarity	NPC604764
0.76	Intermediate Similarity	NPC156804
0.7292	Intermediate Similarity	NPC73310
0.7292	Intermediate Similarity	NPC473529
0.7292	Intermediate Similarity	NPC180363
0.7292	Intermediate Similarity	NPC94875
0.7292	Intermediate Similarity	NPC11332
0.7292	Intermediate Similarity	NPC145914
0.7292	Intermediate Similarity	NPC601174
0.7292	Intermediate Similarity	NPC601403
0.7292	Intermediate Similarity	NPC603568
0.7292	Intermediate Similarity	NPC604330
0.7292	Intermediate Similarity	NPC608300
0.7292	Intermediate Similarity	NPC611200
0.7292	Intermediate Similarity	NPC611571
0.72	Intermediate Similarity	NPC107986
0.72	Intermediate Similarity	NPC223871
0.72	Intermediate Similarity	NPC231009
0.72	Intermediate Similarity	NPC103284
0.72	Intermediate Similarity	NPC110710
0.72	Intermediate Similarity	NPC1083
0.72	Intermediate Similarity	NPC82795
0.72	Intermediate Similarity	NPC286338
0.72	Intermediate Similarity	NPC603931
0.72	Intermediate Similarity	NPC604237
0.7115	Intermediate Similarity	NPC473156
0.7115	Intermediate Similarity	NPC163093
0.7115	Intermediate Similarity	NPC282815
0.7115	Intermediate Similarity	NPC600956
0.7115	Intermediate Similarity	NPC610454
0.7059	Intermediate Similarity	NPC488253
0.7059	Intermediate Similarity	NPC473669
0.7059	Intermediate Similarity	NPC488251
0.7037	Intermediate Similarity	NPC329838
0.7	Intermediate Similarity	NPC606043
0.6981	Remote Similarity	NPC473671
0.6981	Remote Similarity	NPC475268
0.6981	Remote Similarity	NPC470400
0.6981	Remote Similarity	NPC77871
0.6981	Remote Similarity	NPC9678
0.6981	Remote Similarity	NPC319036
0.6981	Remote Similarity	NPC605867
0.6964	Remote Similarity	NPC89001
0.6923	Remote Similarity	NPC232555
0.6923	Remote Similarity	NPC171174
0.6923	Remote Similarity	NPC114694
0.6923	Remote Similarity	NPC485248
0.6923	Remote Similarity	NPC142117
0.6923	Remote Similarity	NPC480249
0.6923	Remote Similarity	NPC485249
0.6923	Remote Similarity	NPC240695
0.6897	Remote Similarity	NPC253801
0.6863	Remote Similarity	NPC329829
0.6852	Remote Similarity	NPC132940
0.6792	Remote Similarity	NPC488632
0.6792	Remote Similarity	NPC477011
0.6786	Remote Similarity	NPC258068
0.6786	Remote Similarity	NPC476583
0.6727	Remote Similarity	NPC20533
0.6667	Remote Similarity	NPC477014
0.6667	Remote Similarity	NPC477013
0.6604	Remote Similarity	NPC182383
0.6557	Remote Similarity	NPC477017
0.6557	Remote Similarity	NPC477016
0.6545	Remote Similarity	NPC178215
0.6538	Remote Similarity	NPC25764
0.6538	Remote Similarity	NPC235809
0.6538	Remote Similarity	NPC39279
0.6538	Remote Similarity	NPC39167
0.6538	Remote Similarity	NPC292809
0.6538	Remote Similarity	NPC202055
0.6538	Remote Similarity	NPC606804
0.6538	Remote Similarity	NPC607425
0.6538	Remote Similarity	NPC608574
0.6481	Remote Similarity	NPC93794
0.6481	Remote Similarity	NPC134865
0.6481	Remote Similarity	NPC473504
0.6481	Remote Similarity	NPC488246
0.6481	Remote Similarity	NPC103523
0.6481	Remote Similarity	NPC144415
0.6481	Remote Similarity	NPC81778
0.6481	Remote Similarity	NPC40066
0.6481	Remote Similarity	NPC488627
0.6481	Remote Similarity	NPC488631
0.6481	Remote Similarity	NPC600524
0.6481	Remote Similarity	NPC608157
0.6481	Remote Similarity	NPC608355
0.6441	Remote Similarity	NPC322529
0.6379	Remote Similarity	NPC480082
0.6364	Remote Similarity	NPC280621
0.6364	Remote Similarity	NPC48338
0.6364	Remote Similarity	NPC241360
0.6364	Remote Similarity	NPC293136
0.6364	Remote Similarity	NPC488628
0.6296	Remote Similarity	NPC81045
0.6296	Remote Similarity	NPC39754
0.6296	Remote Similarity	NPC171135
0.6296	Remote Similarity	NPC61257
0.6296	Remote Similarity	NPC320569
0.6296	Remote Similarity	NPC133730
0.6296	Remote Similarity	NPC191929
0.6296	Remote Similarity	NPC100454
0.6296	Remote Similarity	NPC242364
0.6296	Remote Similarity	NPC172821
0.6296	Remote Similarity	NPC274446
0.6296	Remote Similarity	NPC485251
0.6296	Remote Similarity	NPC151403
0.6296	Remote Similarity	NPC261952
0.6296	Remote Similarity	NPC605171
0.625	Remote Similarity	NPC42598
0.625	Remote Similarity	NPC473687
0.625	Remote Similarity	NPC204686
0.625	Remote Similarity	NPC219498
0.625	Remote Similarity	NPC308412
0.625	Remote Similarity	NPC134885
0.625	Remote Similarity	NPC488247
0.625	Remote Similarity	NPC210218
0.625	Remote Similarity	NPC488248
0.6207	Remote Similarity	NPC120398
0.6207	Remote Similarity	NPC471567
0.6182	Remote Similarity	NPC47937
0.6167	Remote Similarity	NPC480081
0.6167	Remote Similarity	NPC280612
0.614	Remote Similarity	NPC20621
0.614	Remote Similarity	NPC318963
0.614	Remote Similarity	NPC605101
0.6071	Remote Similarity	NPC219652
0.6071	Remote Similarity	NPC473840
0.6034	Remote Similarity	NPC477012
0.5965	Remote Similarity	NPC65930
0.5932	Remote Similarity	NPC130359
0.5932	Remote Similarity	NPC14901
0.5893	Remote Similarity	NPC480080
0.5862	Remote Similarity	NPC134807
0.5862	Remote Similarity	NPC485250
0.5862	Remote Similarity	NPC600188
0.5862	Remote Similarity	NPC602738
0.5862	Remote Similarity	NPC605396
0.5833	Remote Similarity	NPC488623
0.5833	Remote Similarity	NPC488624
0.5833	Remote Similarity	NPC488629
0.58	Remote Similarity	NPC608138
0.5789	Remote Similarity	NPC25703
0.5781	Remote Similarity	NPC279267
0.5763	Remote Similarity	NPC473478
0.5763	Remote Similarity	NPC473651
0.5763	Remote Similarity	NPC66346
0.5667	Remote Similarity	NPC283085
0.5667	Remote Similarity	NPC169511
0.5667	Remote Similarity	NPC287164
0.5667	Remote Similarity	NPC234077
0.5667	Remote Similarity	NPC473995
0.5667	Remote Similarity	NPC488244
0.5645	Remote Similarity	NPC488630
0.5645	Remote Similarity	NPC488625
0.5645	Remote Similarity	NPC488626
0.5593	Remote Similarity	NPC329615
0.5556	Remote Similarity	NPC112685
0.5556	Remote Similarity	NPC477015
0.55	Remote Similarity	NPC20339
0.549	Remote Similarity	NPC609415
0.5484	Remote Similarity	NPC239517
0.5417	Remote Similarity	NPC474705
0.541	Remote Similarity	NPC231096
0.541	Remote Similarity	NPC475581
0.541	Remote Similarity	NPC62118
0.541	Remote Similarity	NPC132496
0.541	Remote Similarity	NPC107717
0.541	Remote Similarity	NPC488252
0.5397	Remote Similarity	NPC473520
0.5397	Remote Similarity	NPC91067
0.5323	Remote Similarity	NPC320458
0.5323	Remote Similarity	NPC233551
0.5323	Remote Similarity	NPC40376
0.5323	Remote Similarity	NPC21208
0.5312	Remote Similarity	NPC473905
0.5246	Remote Similarity	NPC139418
0.5231	Remote Similarity	NPC473663
0.5231	Remote Similarity	NPC473723
0.5231	Remote Similarity	NPC475173
0.5161	Remote Similarity	NPC606740
0.5161	Remote Similarity	NPC608614
0.5077	Remote Similarity	NPC475206

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC309211 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6547
0.1-0.2	2515
0.2-0.3	86
0.3-0.4	2
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