NPASS Compound

Natural Product: NPC11456

Natural Product ID	NPC11456
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Annomolon B/34-Epi-Annomolon B
IUPAC Name	3-[(2R,13R)-2,13-dihydroxy-13-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]-9-oxotridecyl]-5-hydroxy-5-methylfuran-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL450529
PubChem CID	10348777
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 105106 0 0 0 0 0 0 0 0999 V2000 12.8914 -2.3869 0.6110 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2285 -1.0645 0.3747 C 0 0 0 0 0 0 0 0 0 0 0 0 12.3314 -0.6427 -1.0745 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6759 -1.6344 -1.9715 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2359 -1.8140 -1.6536 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4832 -0.4958 -1.7963 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0576 -0.7974 -1.4397 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1601 0.4130 -1.5421 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6421 1.5030 -0.6350 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7551 2.7248 -0.6855 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3695 2.2946 -0.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4066 3.4314 -0.2043 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0833 3.0235 0.3417 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3287 1.9422 -0.3126 C 0 0 1 0 0 0 0 0 0 0 0 0 2.7040 0.5301 0.0438 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2024 0.4211 1.4727 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0643 1.3830 1.4604 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2120 0.8027 1.9508 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8482 -0.2271 1.0888 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2368 0.1503 -0.2622 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2061 1.2163 -0.4895 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5621 1.0975 0.0039 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2193 2.1471 0.1348 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2932 -0.1149 0.3778 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3896 -0.4668 -0.6083 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1394 -1.7177 -0.2170 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1721 -1.9576 -1.3011 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0178 -3.1414 -1.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8427 -3.2759 0.1133 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9259 -2.3270 0.4202 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.5848 -0.8927 0.6210 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8687 -0.1280 0.9195 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3509 0.8279 0.1576 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.5892 1.3533 0.7190 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.7043 0.9703 -0.2492 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.5493 2.7449 0.8836 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.7813 0.6781 1.9239 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.7577 -0.2467 2.0556 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.6138 -1.0720 3.0171 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.5241 -2.8038 1.6185 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0589 0.1889 3.1768 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0202 2.0075 0.2427 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2512 4.2048 0.1211 O 0 0 0 0 0 0 0 0 0 0 0 0 13.3868 -2.7558 -0.3114 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1711 -3.1118 1.0098 H 0 0 0 0 0 0 0 0 0 0 0 0 13.6871 -2.2780 1.3844 H 0 0 0 0 0 0 0 0 0 0 0 0 11.1676 -1.1298 0.6857 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7112 -0.2719 1.0225 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9159 0.3539 -1.2613 H 0 0 0 0 0 0 0 0 0 0 0 0 13.4195 -0.6262 -1.3715 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1539 -2.6464 -1.9197 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7693 -1.2966 -3.0242 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0584 -2.1880 -0.6373 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7577 -2.5535 -2.3581 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9233 0.2439 -1.1102 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5439 -0.1161 -2.8246 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6709 -1.6133 -2.1222 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9445 -1.2104 -0.4228 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1420 0.0317 -1.2940 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1503 0.7528 -2.6227 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6650 1.7857 -0.9675 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6307 1.1019 0.4052 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0924 3.5195 -0.0037 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6397 3.0736 -1.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0220 1.6430 -1.0816 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3817 1.7961 0.7471 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3320 3.9659 -1.1752 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8645 4.2076 0.4850 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0618 2.9108 1.4349 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2009 2.0200 -1.4010 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7056 0.2016 -0.0846 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0107 -0.1256 -0.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0629 0.7770 2.1182 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9348 -0.5867 1.7773 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3254 2.1982 2.2047 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9291 1.6311 2.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0607 -1.0423 0.9697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6395 -0.7189 1.6899 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3120 0.3327 -0.8804 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6557 -0.7912 -0.7490 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2810 1.4460 -1.5964 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7481 2.1838 -0.1055 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7735 -0.0846 1.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6002 -0.9971 0.4401 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0398 -0.5897 -1.6260 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1588 0.3582 -0.6263 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5462 -1.6931 0.7866 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3830 -2.5529 -0.2358 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5034 -2.2292 -2.2099 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6479 -1.0344 -1.6546 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7332 -3.1750 -1.9774 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3806 -4.0554 -1.2778 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2217 -3.3801 1.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3350 -4.3083 0.0430 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7218 -2.3453 -0.3849 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1334 -0.3646 -0.2030 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9055 -0.7568 1.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9164 1.1921 -0.7596 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.8357 -0.1240 -0.1341 H 0 0 0 0 0 0 0 0 0 0 0 0 -14.6583 1.4724 -0.0365 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.3537 1.1409 -1.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.4347 3.0911 0.5728 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6822 -3.7628 1.4766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2217 -0.7618 3.2075 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7480 4.9965 0.4191 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 21 22 1 0 22 23 2 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 2 0 33 34 1 0 34 35 1 0 34 36 1 0 34 37 1 0 37 38 1 0 38 39 2 0 30 40 1 0 18 41 1 0 17 42 1 0 13 43 1 0 42 14 1 0 38 32 1 0 1 44 1 0 1 45 1 0 1 46 1 0 2 47 1 0 2 48 1 0 3 49 1 0 3 50 1 0 4 51 1 0 4 52 1 0 5 53 1 0 5 54 1 0 6 55 1 0 6 56 1 0 7 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 0 11 66 1 0 12 67 1 0 12 68 1 0 13 69 1 1 14 70 1 6 15 71 1 0 15 72 1 0 16 73 1 0 16 74 1 0 17 75 1 1 18 76 1 1 19 77 1 0 19 78 1 0 20 79 1 0 20 80 1 0 21 81 1 0 21 82 1 0 24 83 1 0 24 84 1 0 25 85 1 0 25 86 1 0 26 87 1 0 26 88 1 0 27 89 1 0 27 90 1 0 28 91 1 0 28 92 1 0 29 93 1 0 29 94 1 0 30 95 1 6 31 96 1 0 31 97 1 0 33 98 1 0 35 99 1 0 35100 1 0 35101 1 0 36102 1 0 40103 1 0 41104 1 0 43105 1 0 M END

Standard InCHIKey	GJVIOLYTKAYTOT-QEGRAPCLSA-N
Standard InCHI	InChI=1S/C35H62O8/c1-3-4-5-6-7-8-9-10-11-16-21-30(38)32-23-24-33(42-32)31(39)22-17-20-28(36)18-14-12-13-15-19-29(37)25-27-26-35(2,41)43-34(27)40/h26,29-33,37-39,41H,3-25H2,1-2H3/t29-,30-,31-,32-,33-,35?/m1/s1
SMILES	CCCCCCCCCCCC[C@H]([C@H]1CC[C@H]([C@@H](CCCC(=O)CCCCCC[C@H](CC2=CC(C)(O)OC2=O)O)O)O1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	610.44	Volume:	659.215 ? Van der Waals volume.
Dense:	0.926	LogP:	5.082 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.505 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.746 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	12.0
TPSA:	133.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.064	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.659	Fsp³:	0.886
MCE-18:	36.576 ? 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:	0.667	Fluc inhibitor:	0.02 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.483	Promiscuous compounds:	0.563

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.16	MDCK Permeability:	-4.837
Pgp-inhibitor:	0.0	Pgp-substrate:	0.123
PAMPA:	0.589 ? 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):	0.074
20% Bioavailability (F20%):	0.776	30% Bioavailability (F30%):	0.985
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.723
Plasma Protein Binding (PPB):	93.739%	Volume Distribution (VD):	0.204
Fu:	5.802% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.597
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.057
BSEP inhibitor:	0.941

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.994	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.13	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.026	CYP3A4-substrate:	0.011
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.026 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.719

Half-life (T1/2):

1.207

ADMET: Toxicity

hERG Blockers:	0.439	hERG Blockers (10um):	0.736
Human Hepatotoxicity (H-HT):	0.622	Drug-induced Liver Injury (DILI):	0.061
AMES Toxicity:	0.079	Rat Oral Acute Toxicity:	0.032
Maximum Recommended Daily Dose:	0.653	Skin Sensitization:	0.997
Carcinogencity:	0.246	Eye Corrosion:	0.038
Eye Irritation:	0.865	Respiratory Toxicity:	0.909
Drug-induced Neurotoxicity:	0.015	Ototoxicity:	0.673
Hematotoxicity:	0.214	Drug-induced Nephrotoxicity:	0.835
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.058
A549 Cytotoxicity:	0.699	Hek293 Cytotoxicity:	0.241
BCF:	1.294 ? 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:	4.889 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.108 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.0 ? 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
NPO26361	Annona cherimolia	Species	Annonaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[11325235]
NPO26361	Annona cherimolia	Species	Annonaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[14575439]
NPO26361	Annona cherimolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26361	Annona cherimolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26361	Annona cherimolia	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26361	Annona cherimolia	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

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

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	=	0.07	ug.mL-1	PMID[14575439]

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 NPC11456 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	17278
0.1-0.2	30533
0.2-0.3	1760
0.3-0.4	74
0.4-0.5	93
0.5-0.6	75
0.6-0.7	21
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8039	Intermediate Similarity	NPC478998
0.7692	Intermediate Similarity	NPC473904
0.7358	Intermediate Similarity	NPC473687
0.7358	Intermediate Similarity	NPC204686
0.7358	Intermediate Similarity	NPC219498
0.7358	Intermediate Similarity	NPC308412
0.7358	Intermediate Similarity	NPC134885
0.7358	Intermediate Similarity	NPC488247
0.7358	Intermediate Similarity	NPC210218
0.7358	Intermediate Similarity	NPC488248
0.6909	Remote Similarity	NPC134807
0.6316	Remote Similarity	NPC477010
0.6226	Remote Similarity	NPC606043
0.6207	Remote Similarity	NPC139418
0.6111	Remote Similarity	NPC107986
0.6111	Remote Similarity	NPC223871
0.6111	Remote Similarity	NPC231009
0.6111	Remote Similarity	NPC103284
0.6111	Remote Similarity	NPC110710
0.6111	Remote Similarity	NPC1083
0.6111	Remote Similarity	NPC82795
0.6111	Remote Similarity	NPC286338
0.6111	Remote Similarity	NPC603931
0.6111	Remote Similarity	NPC604237
0.6102	Remote Similarity	NPC130359
0.6102	Remote Similarity	NPC14901
0.6071	Remote Similarity	NPC144415
0.6071	Remote Similarity	NPC608157
0.6	Remote Similarity	NPC488253
0.6	Remote Similarity	NPC473669
0.6	Remote Similarity	NPC488251
0.5893	Remote Similarity	NPC232555
0.5893	Remote Similarity	NPC171174
0.5893	Remote Similarity	NPC114694
0.5893	Remote Similarity	NPC485248
0.5893	Remote Similarity	NPC142117
0.5893	Remote Similarity	NPC480249
0.5893	Remote Similarity	NPC485249
0.5893	Remote Similarity	NPC240695
0.5789	Remote Similarity	NPC488632
0.5789	Remote Similarity	NPC134865
0.5789	Remote Similarity	NPC103523
0.5789	Remote Similarity	NPC488627
0.5789	Remote Similarity	NPC488631
0.569	Remote Similarity	NPC280621
0.569	Remote Similarity	NPC48338
0.569	Remote Similarity	NPC488628
0.5667	Remote Similarity	NPC477012
0.5614	Remote Similarity	NPC81045
0.5614	Remote Similarity	NPC39754
0.5614	Remote Similarity	NPC171135
0.5614	Remote Similarity	NPC182383
0.5614	Remote Similarity	NPC61257
0.5614	Remote Similarity	NPC320569
0.5614	Remote Similarity	NPC133730
0.5614	Remote Similarity	NPC191929
0.5614	Remote Similarity	NPC100454
0.5614	Remote Similarity	NPC242364
0.5614	Remote Similarity	NPC172821
0.5614	Remote Similarity	NPC274446
0.5614	Remote Similarity	NPC485251
0.5614	Remote Similarity	NPC151403
0.5614	Remote Similarity	NPC261952
0.5614	Remote Similarity	NPC605171
0.5593	Remote Similarity	NPC178215
0.5556	Remote Similarity	NPC280612
0.5517	Remote Similarity	NPC93794
0.5517	Remote Similarity	NPC473504
0.5517	Remote Similarity	NPC81778
0.5517	Remote Similarity	NPC40066
0.55	Remote Similarity	NPC20621
0.55	Remote Similarity	NPC318963
0.55	Remote Similarity	NPC488250
0.55	Remote Similarity	NPC605101
0.55	Remote Similarity	NPC605396
0.5455	Remote Similarity	NPC482766
0.5455	Remote Similarity	NPC477017
0.5455	Remote Similarity	NPC477016
0.541	Remote Similarity	NPC69082
0.541	Remote Similarity	NPC488249
0.5333	Remote Similarity	NPC42598
0.5263	Remote Similarity	NPC100921
0.5263	Remote Similarity	NPC475159
0.5263	Remote Similarity	NPC131002
0.5263	Remote Similarity	NPC473780
0.5263	Remote Similarity	NPC477018
0.5263	Remote Similarity	NPC604521
0.5254	Remote Similarity	NPC47937
0.5254	Remote Similarity	NPC477011
0.5246	Remote Similarity	NPC602738
0.5238	Remote Similarity	NPC488623
0.5238	Remote Similarity	NPC488624
0.5238	Remote Similarity	NPC488629
0.5231	Remote Similarity	NPC477015
0.5161	Remote Similarity	NPC473478
0.5161	Remote Similarity	NPC473651
0.5161	Remote Similarity	NPC66346
0.5085	Remote Similarity	NPC156804
0.5079	Remote Similarity	NPC283085
0.5079	Remote Similarity	NPC169511
0.5079	Remote Similarity	NPC287164
0.5079	Remote Similarity	NPC234077
0.5079	Remote Similarity	NPC488244
0.5077	Remote Similarity	NPC488630
0.5077	Remote Similarity	NPC488625
0.5077	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 NPC11456 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6450
0.1-0.2	2646
0.2-0.3	53
0.3-0.4	1
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