NPASS Compound

Natural Product: NPC481488

Natural Product ID	NPC481488
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	XCZFWSQANJYCRY-BBRQKAMZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11125536
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0002967] Hexacarboxylic acids and derivatives

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 102106 0 0 0 0 0 0 0 0999 V2000 -1.3889 -4.9628 1.9517 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7517 -3.7194 2.7743 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8633 -2.9577 2.0736 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0685 -3.8863 1.9412 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5176 -2.3872 0.7968 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0847 -2.8012 -0.2507 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5496 -1.3626 0.6752 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3051 -0.8930 -0.6780 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3031 0.1846 -0.7845 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0513 -0.2392 -0.2075 C 0 0 2 0 0 0 0 0 0 0 0 0 2.2274 0.2176 -1.0562 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1816 -0.2562 -2.4671 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7769 -0.3151 -3.0294 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3838 -1.7084 -3.2644 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0590 0.6045 -2.2448 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3684 0.9782 -2.8243 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4535 2.4074 -2.2428 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6948 2.3035 -0.7797 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7731 1.3828 -0.0230 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4662 1.0639 1.1632 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0086 1.4256 2.4192 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0721 2.0476 2.5111 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7333 1.1157 3.6355 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9519 0.4781 3.6677 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6249 0.1923 4.8327 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0905 0.5435 6.0493 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8701 1.1850 6.0646 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2109 1.4625 4.8872 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5424 3.5852 -0.1760 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5436 4.2793 0.4547 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6768 3.7547 0.5070 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2282 5.6084 1.0379 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0519 2.8694 -2.5562 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0529 3.3482 -4.0045 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3801 4.0763 -1.7300 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7007 1.8097 -2.2251 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3288 1.0000 -4.2413 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2803 0.4713 -5.0595 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2811 -0.0843 -4.5498 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1724 0.5309 -6.5344 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8792 0.2699 -4.3228 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3586 -0.4589 -0.4604 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4161 0.2202 0.1232 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3447 1.4894 0.1104 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5426 -0.4712 0.7165 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5461 -1.8485 0.6917 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5968 -2.5230 1.2449 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6188 -1.8061 1.8096 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6203 -0.4242 1.8371 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5605 0.2570 1.2791 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1681 -1.6055 0.0341 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4818 -2.0946 1.2678 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6581 -1.2497 2.2002 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6217 -3.5563 1.5413 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1905 -5.7063 2.0507 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4796 -5.3770 2.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2203 -4.6177 0.9236 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0957 -4.0833 3.7580 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8733 -3.0722 2.9358 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1986 -2.1955 2.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1919 -4.5128 2.8371 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9593 -3.2288 1.8225 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9633 -4.5003 1.0335 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3589 -0.5983 -0.9714 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1296 -1.8144 -1.2435 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2278 0.2877 0.7800 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4624 1.2853 -0.9074 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8535 0.4115 -3.0587 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6501 -1.2688 -2.5496 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6647 -1.8702 -3.5692 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7538 -2.4641 -2.5210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9457 -2.0471 -4.1992 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2633 0.4815 -2.4653 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2451 2.9918 -2.6991 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7582 2.0201 -0.6249 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1401 1.9203 0.3387 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4018 0.1882 2.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5765 -0.3080 4.8179 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5624 0.3517 7.0068 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4340 1.4701 7.0204 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2536 1.9639 4.8813 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3293 6.4329 0.3128 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8254 5.8542 1.9228 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1506 5.6514 1.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2028 4.4757 -4.0536 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9628 2.9730 -4.5132 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8831 3.2214 -4.5739 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3949 4.8784 -1.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8192 3.8553 -0.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2298 4.5487 -2.3175 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8193 -0.2200 -7.0377 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1468 0.3636 -6.9031 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4958 1.5215 -6.9117 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6188 -0.1722 -4.7954 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7425 -2.4146 0.2480 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5923 -3.5974 1.2214 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4440 -2.3597 2.2437 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4451 0.1261 2.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5541 1.3527 1.2962 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7251 -3.7688 1.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3704 -3.8354 2.5652 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1283 -4.1461 0.7606 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 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 9 8 1 6 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 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 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 18 29 1 0 29 30 1 0 30 31 2 0 30 32 1 0 17 33 1 0 33 34 1 0 33 35 1 0 33 36 1 0 16 37 1 0 37 38 1 0 38 39 2 0 38 40 1 0 13 41 1 6 11 42 1 0 42 43 1 0 43 44 2 0 43 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 48 49 1 0 49 50 2 0 10 51 1 0 51 52 1 0 52 53 2 0 52 54 1 0 19 9 1 0 28 23 1 0 50 45 1 0 15 9 1 0 15 36 1 1 1 55 1 0 1 56 1 0 1 57 1 0 2 58 1 0 2 59 1 0 3 60 1 0 4 61 1 0 4 62 1 0 4 63 1 0 8 64 1 0 8 65 1 0 10 66 1 1 11 67 1 6 12 68 1 0 12 69 1 0 14 70 1 0 14 71 1 0 14 72 1 0 16 73 1 6 17 74 1 6 18 75 1 6 19 76 1 1 24 77 1 0 25 78 1 0 26 79 1 0 27 80 1 0 28 81 1 0 32 82 1 0 32 83 1 0 32 84 1 0 34 85 1 0 34 86 1 0 34 87 1 0 35 88 1 0 35 89 1 0 35 90 1 0 40 91 1 0 40 92 1 0 40 93 1 0 41 94 1 0 46 95 1 0 47 96 1 0 48 97 1 0 49 98 1 0 50 99 1 0 54100 1 0 54101 1 0 54102 1 0 M END

Standard InCHIKey	XCZFWSQANJYCRY-BBRQKAMZSA-N
Standard InCHI	InChI=1S/C40H48O14/c1-9-22(2)34(44)48-21-39-31(50-24(4)42)28(52-35(45)26-16-12-10-13-17-26)20-38(8,47)40(39)32(51-25(5)43)29(37(6,7)54-40)30(49-23(3)41)33(39)53-36(46)27-18-14-11-15-19-27/h10-19,22,28-33,47H,9,20-21H2,1-8H3/t22?,28-,29+,30-,31-,32+,33+,38-,39-,40-/m0/s1
SMILES	CCC(C)C(=O)OC[C@]12[C@H]([C@H](C[C@@](C)([C@]32[C@@H]([C@@H]([C@@H]([C@H]1OC(=O)c1ccccc1)OC(=O)C)C(C)(C)O3)OC(=O)C)O)OC(=O)c1ccccc1)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	752.3	Volume:	749.039 ? Van der Waals volume.
Dense:	1.004	LogP:	3.979 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.49 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.926 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	32.0
TPSA:	187.26 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.255	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.19	Fsp³:	0.55
MCE-18:	182.903 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.501	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.204 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.115	Promiscuous compounds:	0.158

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.287	MDCK Permeability:	-4.83
Pgp-inhibitor:	0.915	Pgp-substrate:	0.115
PAMPA:	0.171 ? 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):	0.0
20% Bioavailability (F20%):	0.025	30% Bioavailability (F30%):	0.054
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.985	MRP1:	1.0
Plasma Protein Binding (PPB):	83.152%	Volume Distribution (VD):	-0.44
Fu:	18.106% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.51	BCRP inhibitor:	0.001
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.11
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.707	CYP3A4-substrate:	0.691
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

2.378

Half-life (T1/2):

1.097

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.296
Human Hepatotoxicity (H-HT):	0.121	Drug-induced Liver Injury (DILI):	0.89
AMES Toxicity:	0.734	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.249	Skin Sensitization:	0.998
Carcinogencity:	0.762	Eye Corrosion:	0.0
Eye Irritation:	0.174	Respiratory Toxicity:	0.031
Drug-induced Neurotoxicity:	0.587	Ototoxicity:	0.287
Hematotoxicity:	0.061	Drug-induced Nephrotoxicity:	0.71
Genotoxicity:	0.386	RPMI-8226 Immunitoxicity:	0.11
A549 Cytotoxicity:	0.233	Hek293 Cytotoxicity:	0.536
BCF:	0.656 ? 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:	3.562 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.005 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.611 ? 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
NPO17696	Crossopetalum tonduzii	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[12932121]
NPO17696	Crossopetalum tonduzii	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17696	Crossopetalum tonduzii	Species	n.a.	n.a.	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
Activity	8

Activity Type	# Activity
Cell line	4
Others	4

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
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[12932121]
NPT80	Cell line	Raji	Homo sapiens	Activity	>	80.0	%	PMID[12932121]
NPT2	Others	Unspecified	n.a.	Activity	=	4.6	%	PMID[12932121]
NPT2	Others	Unspecified	n.a.	Activity	=	33.8	%	PMID[12932121]
NPT2	Others	Unspecified	n.a.	Activity	=	75.9	%	PMID[12932121]
NPT2	Others	Unspecified	n.a.	Activity	=	96.0	%	PMID[12932121]

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 NPC481488 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	12526
0.1-0.2	34957
0.2-0.3	1751
0.3-0.4	428
0.4-0.5	130
0.5-0.6	41
0.6-0.7	15
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9552	High Similarity	NPC481489
0.9104	High Similarity	NPC472569
0.8824	High Similarity	NPC16912
0.8286	Intermediate Similarity	NPC11685
0.8286	Intermediate Similarity	NPC472570
0.76	Intermediate Similarity	NPC481486
0.7324	Intermediate Similarity	NPC483886
0.6974	Remote Similarity	NPC70716
0.6883	Remote Similarity	NPC481490
0.6842	Remote Similarity	NPC57628
0.6795	Remote Similarity	NPC479042
0.6753	Remote Similarity	NPC97667
0.6667	Remote Similarity	NPC472568
0.6625	Remote Similarity	NPC488917
0.6622	Remote Similarity	NPC281717
0.6579	Remote Similarity	NPC471104
0.6538	Remote Similarity	NPC95265
0.6456	Remote Similarity	NPC471102
0.641	Remote Similarity	NPC479043
0.625	Remote Similarity	NPC282239
0.6098	Remote Similarity	NPC481487
0.6	Remote Similarity	NPC610134
0.5909	Remote Similarity	NPC30171
0.5843	Remote Similarity	NPC176413
0.5843	Remote Similarity	NPC483885
0.5843	Remote Similarity	NPC479045
0.5823	Remote Similarity	NPC472572
0.5769	Remote Similarity	NPC473060
0.5696	Remote Similarity	NPC147880
0.5667	Remote Similarity	NPC294512
0.5625	Remote Similarity	NPC471101
0.5625	Remote Similarity	NPC137718
0.5604	Remote Similarity	NPC483868
0.557	Remote Similarity	NPC51314
0.5542	Remote Similarity	NPC106895
0.55	Remote Similarity	NPC163719
0.55	Remote Similarity	NPC90257
0.55	Remote Similarity	NPC200471
0.55	Remote Similarity	NPC95810
0.55	Remote Similarity	NPC69357
0.55	Remote Similarity	NPC472575
0.5432	Remote Similarity	NPC147217
0.5432	Remote Similarity	NPC148062
0.5366	Remote Similarity	NPC171207
0.5281	Remote Similarity	NPC479041
0.5238	Remote Similarity	NPC252314
0.519	Remote Similarity	NPC481047
0.519	Remote Similarity	NPC481045
0.5185	Remote Similarity	NPC472577
0.5176	Remote Similarity	NPC96903
0.5169	Remote Similarity	NPC125106
0.5169	Remote Similarity	NPC472573
0.5155	Remote Similarity	NPC6981
0.5122	Remote Similarity	NPC483845
0.5122	Remote Similarity	NPC4341
0.5119	Remote Similarity	NPC479044
0.5119	Remote Similarity	NPC483844
0.5116	Remote Similarity	NPC483848
0.5062	Remote Similarity	NPC90614
0.5057	Remote Similarity	NPC294803
0.5057	Remote Similarity	NPC481062
0.5057	Remote Similarity	NPC481058
0.5057	Remote Similarity	NPC481060

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC481488 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3721
0.1-0.2	5287
0.2-0.3	142
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