NPASS Compound

Natural Product: NPC477011

Natural Product ID	NPC477011
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Plagionicin C
IUPAC Name	(2S)-2-methyl-4-[(13S)-2,3,9,13-tetrahydroxy-13-[(2S,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]tridecyl]-2H-furan-5-one
Synonyms	Plagionicin C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44583894
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 107108 0 0 0 0 0 0 0 0999 V2000 -11.5911 -2.1607 3.2085 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.6569 -2.9163 2.3106 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2651 -2.9814 2.8860 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6611 -1.6066 3.0892 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5725 -0.8548 1.7696 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9513 0.4981 2.0736 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8278 1.3176 0.8324 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9798 0.6209 -0.1868 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5981 0.3932 0.3560 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7501 -0.3158 -0.6813 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3382 -0.5588 -0.2430 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5440 0.6689 0.0626 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3975 1.5550 -1.1486 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5594 2.7710 -0.7489 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1659 2.3138 -0.3990 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6969 3.4013 -1.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1789 3.8009 -2.2092 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4605 3.6679 -1.7674 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1122 2.7450 -3.2622 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3743 3.1652 -4.0564 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6365 2.1175 -5.0831 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0243 0.7945 -4.5050 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3395 0.9224 -3.7926 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8692 -0.3309 -3.1947 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0622 -0.9943 -2.1506 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8390 -0.1453 -0.9229 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1053 0.2555 -0.2470 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9198 -0.9272 0.2245 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1601 -0.3275 0.8791 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0597 -1.4446 1.3968 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2718 -0.8499 2.0774 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1579 -1.9147 2.5939 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4465 -2.0174 3.9007 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3456 -3.1569 4.1403 C 0 0 1 0 0 0 0 0 0 0 0 0 10.5754 -3.7492 2.8776 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8533 -2.9835 1.9515 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8501 -3.2439 0.7195 O 0 0 0 0 0 0 0 0 0 0 0 0 11.7240 -2.6955 4.6381 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4465 -2.2915 0.3726 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7724 0.5208 1.9020 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2878 1.3393 -4.7577 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8891 2.8270 -4.2729 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6791 2.0344 -1.5206 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.8813 -1.2203 2.7271 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1329 -1.9626 4.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.5268 -2.7318 3.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6550 -2.4989 1.2715 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0265 -3.9550 2.2164 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2721 -3.5089 3.8375 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6211 -3.5738 2.1872 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6273 -1.7399 3.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2264 -1.0020 3.8060 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8516 -1.3969 1.1144 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5654 -0.7281 1.3202 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9552 0.3779 2.5373 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6051 1.0322 2.8310 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8192 1.5118 0.3582 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3386 2.2991 1.0644 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9452 1.2626 -1.1090 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4292 -0.3512 -0.5398 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1548 1.3532 0.6309 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6147 -0.3016 1.2451 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2120 -1.3469 -0.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8476 0.1304 -1.6711 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2937 -1.2873 0.6183 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8483 -1.1436 -1.0781 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5494 0.3984 0.4747 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0175 1.2917 0.8594 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9208 0.9899 -1.9472 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0161 3.2057 0.1566 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0188 2.2321 0.6959 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0334 1.3728 -0.9255 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6756 3.0513 -1.3401 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7701 4.2631 -0.3079 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1144 4.7728 -2.6012 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2531 1.7541 -2.9022 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1609 3.3357 -3.3216 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0654 4.1419 -4.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5101 2.4403 -5.7241 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7758 2.0202 -5.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1628 0.0622 -5.3506 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2356 0.3417 -3.8618 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2638 1.7560 -3.0690 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9394 -0.2114 -2.8620 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9610 -1.0713 -4.0493 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5247 -1.9629 -1.8960 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0599 -1.2325 -2.5679 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2591 0.7526 -1.1975 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2283 -0.7336 -0.2140 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8543 0.8726 0.6389 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7765 0.8618 -0.8926 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3353 -1.5153 0.9466 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1928 -1.5346 -0.6566 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7619 0.2429 0.1708 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4837 -2.0292 2.1320 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8026 -0.2542 1.2736 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9715 -0.1316 2.8609 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0836 -1.3674 4.6880 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9477 -3.8887 4.8884 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1123 -1.9885 3.8577 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6279 -2.2216 5.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3671 -3.6086 4.6665 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1711 -1.9823 -0.5358 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5179 1.1569 2.1357 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4987 0.5773 -5.3520 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6948 2.3534 -3.9342 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6947 3.0042 -1.5046 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 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 35 36 1 0 36 37 2 0 34 38 1 0 30 39 1 0 29 40 1 0 23 41 1 0 19 42 1 0 13 43 1 0 18 14 1 0 36 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 6 14 70 1 1 15 71 1 0 15 72 1 0 16 73 1 0 16 74 1 0 17 75 1 6 19 76 1 1 20 77 1 0 20 78 1 0 21 79 1 0 21 80 1 0 22 81 1 0 22 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 0 30 95 1 0 31 96 1 0 31 97 1 0 33 98 1 0 34 99 1 1 38100 1 0 38101 1 0 38102 1 0 39103 1 0 40104 1 0 41105 1 0 42106 1 0 43107 1 0 M END

Standard InCHIKey	MFTGRNYZFKLFOT-FGDAHWEPSA-N
Standard InCHI	InChI=1S/C35H64O8/c1-3-4-5-6-7-8-9-10-11-14-20-30(38)33-22-23-34(43-33)31(39)21-16-18-28(36)17-13-12-15-19-29(37)32(40)25-27-24-26(2)42-35(27)41/h24,26,28-34,36-40H,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](CCCC(CCCCCC(C(CC2=C[C@@H](OC2=O)C)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	612.46	Volume:	661.852 ? Van der Waals volume.
Dense:	0.925	LogP:	4.922 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.378 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.579 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	26.0	Rigid Bonds:	11.0
TPSA:	136.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	5.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.059	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.803	Fsp³:	0.914
MCE-18:	34.388 ? 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:	0.685	Fluc inhibitor:	0.009 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.072 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.392	Promiscuous compounds:	0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.227	MDCK Permeability:	-4.851
Pgp-inhibitor:	0.0	Pgp-substrate:	0.776
PAMPA:	0.359 ? 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):	0.775
20% Bioavailability (F20%):	0.987	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.883
Plasma Protein Binding (PPB):	93.633%	Volume Distribution (VD):	0.362
Fu:	5.75% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.478
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.281
BSEP inhibitor:	0.894

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:	0.855
CYP3A4-inhibitor:	0.415	CYP3A4-substrate:	0.038
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.933
HLM stability:	0.001 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

6.634

Half-life (T1/2):

1.162

ADMET: Toxicity

hERG Blockers:	0.398	hERG Blockers (10um):	0.855
Human Hepatotoxicity (H-HT):	0.588	Drug-induced Liver Injury (DILI):	0.083
AMES Toxicity:	0.137	Rat Oral Acute Toxicity:	0.035
Maximum Recommended Daily Dose:	0.919	Skin Sensitization:	0.994
Carcinogencity:	0.221	Eye Corrosion:	0.0
Eye Irritation:	0.086	Respiratory Toxicity:	0.813
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.99
Hematotoxicity:	0.026	Drug-induced Nephrotoxicity:	0.927
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.817	Hek293 Cytotoxicity:	0.283
BCF:	1.388 ? 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:	4.892 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.076 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.153 ? 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
NPO22123	Disepalum plagioneurum	Species	Annonaceae	Eukaryota	leaves	Tam Kim, Cao Bang Province, in North Vietnam	2000-JUN	PMID[16989521]
NPO22123	Disepalum plagioneurum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22123	Disepalum plagioneurum	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

Activity Type	# Activity
Cell line	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
NPT91	Cell line	KB	Homo sapiens	IC50	=	6	nM	PMID[16989521]

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 NPC477011 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	16615
0.1-0.2	29935
0.2-0.3	2975
0.3-0.4	100
0.4-0.5	24
0.5-0.6	16
0.6-0.7	70
0.7-0.8	0
0.8-0.85	22
0.85-0.9	2
0.9-0.95	4
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9111	High Similarity	NPC134865
0.9111	High Similarity	NPC103523
0.9111	High Similarity	NPC488627
0.9111	High Similarity	NPC488631
0.8667	High Similarity	NPC488253
0.8667	High Similarity	NPC488251
0.8444	Intermediate Similarity	NPC107986
0.8444	Intermediate Similarity	NPC223871
0.8444	Intermediate Similarity	NPC231009
0.8444	Intermediate Similarity	NPC103284
0.8444	Intermediate Similarity	NPC110710
0.8444	Intermediate Similarity	NPC1083
0.8444	Intermediate Similarity	NPC82795
0.8444	Intermediate Similarity	NPC286338
0.8444	Intermediate Similarity	NPC603931
0.8444	Intermediate Similarity	NPC604237
0.8298	Intermediate Similarity	NPC488632
0.8261	Intermediate Similarity	NPC473669
0.8222	Intermediate Similarity	NPC606043
0.8163	Intermediate Similarity	NPC329838
0.8085	Intermediate Similarity	NPC232555
0.8085	Intermediate Similarity	NPC171174
0.8085	Intermediate Similarity	NPC114694
0.8085	Intermediate Similarity	NPC485248
0.8085	Intermediate Similarity	NPC142117
0.8085	Intermediate Similarity	NPC480249
0.8085	Intermediate Similarity	NPC485249
0.8085	Intermediate Similarity	NPC240695
0.7959	Intermediate Similarity	NPC178215
0.7708	Intermediate Similarity	NPC182383
0.766	Intermediate Similarity	NPC329829
0.766	Intermediate Similarity	NPC100921
0.766	Intermediate Similarity	NPC475159
0.766	Intermediate Similarity	NPC131002
0.766	Intermediate Similarity	NPC473780
0.766	Intermediate Similarity	NPC477018
0.766	Intermediate Similarity	NPC604521
0.7647	Intermediate Similarity	NPC473478
0.7647	Intermediate Similarity	NPC69082
0.7647	Intermediate Similarity	NPC473651
0.7647	Intermediate Similarity	NPC488249
0.7647	Intermediate Similarity	NPC66346
0.7551	Intermediate Similarity	NPC93794
0.7551	Intermediate Similarity	NPC473504
0.7551	Intermediate Similarity	NPC81778
0.7551	Intermediate Similarity	NPC40066
0.75	Intermediate Similarity	NPC283085
0.7451	Intermediate Similarity	NPC488250
0.74	Intermediate Similarity	NPC280621
0.74	Intermediate Similarity	NPC48338
0.74	Intermediate Similarity	NPC488628
0.7347	Intermediate Similarity	NPC81045
0.7347	Intermediate Similarity	NPC39754
0.7347	Intermediate Similarity	NPC171135
0.7347	Intermediate Similarity	NPC61257
0.7347	Intermediate Similarity	NPC320569
0.7347	Intermediate Similarity	NPC133730
0.7347	Intermediate Similarity	NPC191929
0.7347	Intermediate Similarity	NPC100454
0.7347	Intermediate Similarity	NPC242364
0.7347	Intermediate Similarity	NPC172821
0.7347	Intermediate Similarity	NPC156804
0.7347	Intermediate Similarity	NPC274446
0.7347	Intermediate Similarity	NPC485251
0.7347	Intermediate Similarity	NPC151403
0.7347	Intermediate Similarity	NPC261952
0.7347	Intermediate Similarity	NPC605171
0.7255	Intermediate Similarity	NPC42598
0.7255	Intermediate Similarity	NPC473687
0.7255	Intermediate Similarity	NPC204686
0.7255	Intermediate Similarity	NPC219498
0.7255	Intermediate Similarity	NPC308412
0.7255	Intermediate Similarity	NPC134885
0.7255	Intermediate Similarity	NPC488247
0.7255	Intermediate Similarity	NPC210218
0.7255	Intermediate Similarity	NPC488248
0.72	Intermediate Similarity	NPC47937
0.717	Intermediate Similarity	NPC231096
0.717	Intermediate Similarity	NPC475581
0.717	Intermediate Similarity	NPC62118
0.717	Intermediate Similarity	NPC132496
0.717	Intermediate Similarity	NPC107717
0.717	Intermediate Similarity	NPC488252
0.7115	Intermediate Similarity	NPC20621
0.7115	Intermediate Similarity	NPC318963
0.7115	Intermediate Similarity	NPC605101
0.7091	Intermediate Similarity	NPC91067
0.7059	Intermediate Similarity	NPC473671
0.7059	Intermediate Similarity	NPC219652
0.7059	Intermediate Similarity	NPC475268
0.7059	Intermediate Similarity	NPC473840
0.7059	Intermediate Similarity	NPC470400
0.7059	Intermediate Similarity	NPC77871
0.7059	Intermediate Similarity	NPC9678
0.7059	Intermediate Similarity	NPC319036
0.7059	Intermediate Similarity	NPC604764
0.7059	Intermediate Similarity	NPC605867
0.7037	Intermediate Similarity	NPC233551
0.7037	Intermediate Similarity	NPC40376
0.7037	Intermediate Similarity	NPC21208
0.7021	Intermediate Similarity	NPC73310
0.7021	Intermediate Similarity	NPC473529
0.7021	Intermediate Similarity	NPC180363
0.7021	Intermediate Similarity	NPC94875
0.7021	Intermediate Similarity	NPC11332
0.7021	Intermediate Similarity	NPC145914
0.7021	Intermediate Similarity	NPC601174
0.7021	Intermediate Similarity	NPC601403
0.7021	Intermediate Similarity	NPC603568
0.7021	Intermediate Similarity	NPC604330
0.7021	Intermediate Similarity	NPC608300
0.7021	Intermediate Similarity	NPC611200
0.7021	Intermediate Similarity	NPC611571
0.6981	Remote Similarity	NPC477012
0.6889	Remote Similarity	NPC608138
0.6863	Remote Similarity	NPC473649
0.6863	Remote Similarity	NPC473156
0.6863	Remote Similarity	NPC154097
0.6863	Remote Similarity	NPC163093
0.6863	Remote Similarity	NPC159750
0.6863	Remote Similarity	NPC73248
0.6863	Remote Similarity	NPC282815
0.6863	Remote Similarity	NPC470401
0.6863	Remote Similarity	NPC600524
0.6863	Remote Similarity	NPC600956
0.6863	Remote Similarity	NPC608355
0.6863	Remote Similarity	NPC610454
0.6852	Remote Similarity	NPC258068
0.6852	Remote Similarity	NPC130359
0.6852	Remote Similarity	NPC14901
0.6852	Remote Similarity	NPC476583
0.6852	Remote Similarity	NPC606740
0.6852	Remote Similarity	NPC608614
0.6792	Remote Similarity	NPC309211
0.6792	Remote Similarity	NPC20533
0.6792	Remote Similarity	NPC134807
0.6792	Remote Similarity	NPC477010
0.6792	Remote Similarity	NPC602738
0.6786	Remote Similarity	NPC480081
0.6731	Remote Similarity	NPC480079
0.6727	Remote Similarity	NPC488623
0.6727	Remote Similarity	NPC488624
0.6727	Remote Similarity	NPC488629
0.6604	Remote Similarity	NPC65930
0.6604	Remote Similarity	NPC132940
0.6545	Remote Similarity	NPC169511
0.6545	Remote Similarity	NPC287164
0.6545	Remote Similarity	NPC234077
0.6538	Remote Similarity	NPC488246
0.6538	Remote Similarity	NPC480080
0.6531	Remote Similarity	NPC112685
0.6491	Remote Similarity	NPC488630
0.6491	Remote Similarity	NPC488625
0.6491	Remote Similarity	NPC488626
0.6429	Remote Similarity	NPC477014
0.6429	Remote Similarity	NPC477013
0.6415	Remote Similarity	NPC25703
0.6364	Remote Similarity	NPC20339
0.6333	Remote Similarity	NPC279267
0.6316	Remote Similarity	NPC239517
0.6296	Remote Similarity	NPC473904
0.6275	Remote Similarity	NPC25764
0.6275	Remote Similarity	NPC235809
0.6275	Remote Similarity	NPC39279
0.6275	Remote Similarity	NPC39167
0.6275	Remote Similarity	NPC292809
0.6275	Remote Similarity	NPC202055
0.6275	Remote Similarity	NPC606804
0.6275	Remote Similarity	NPC607425
0.6275	Remote Similarity	NPC608574
0.6226	Remote Similarity	NPC144415
0.6226	Remote Similarity	NPC607439
0.6226	Remote Similarity	NPC608157
0.6182	Remote Similarity	NPC329615
0.6182	Remote Similarity	NPC485250
0.617	Remote Similarity	NPC609415
0.614	Remote Similarity	NPC89001
0.6111	Remote Similarity	NPC241360
0.6111	Remote Similarity	NPC293136
0.6102	Remote Similarity	NPC473905
0.6	Remote Similarity	NPC473663
0.6	Remote Similarity	NPC473723
0.6	Remote Similarity	NPC475173
0.5965	Remote Similarity	NPC120398
0.5965	Remote Similarity	NPC471567
0.5932	Remote Similarity	NPC280612
0.5862	Remote Similarity	NPC480082
0.5833	Remote Similarity	NPC253801
0.5806	Remote Similarity	NPC477017
0.5806	Remote Similarity	NPC477016
0.569	Remote Similarity	NPC488244
0.5614	Remote Similarity	NPC605396
0.5593	Remote Similarity	NPC320458
0.5556	Remote Similarity	NPC482766
0.5517	Remote Similarity	NPC473707
0.5517	Remote Similarity	NPC139418
0.5424	Remote Similarity	NPC473995
0.5357	Remote Similarity	NPC482767
0.5357	Remote Similarity	NPC475260

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477011 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6349
0.1-0.2	2743
0.2-0.3	58
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data