NPASS Compound

Natural Product: NPC469561

Natural Product ID	NPC469561
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl Ganoderate E
IUPAC Name	methyl (6R)-2-methyl-4-oxo-6-[(5R,10S,13R,14R,17R)-4,4,10,13,14-pentamethyl-3,7,11,15-tetraoxo-2,5,6,12,16,17-hexahydro-1H-cyclopenta[a]phenanthren-17-yl]heptanoate
Synonyms	Methyl Ganoderate E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1087516
PubChem CID	21632959
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 80 83 0 0 0 0 0 0 0 0999 V2000 3.2266 -0.7713 2.1485 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4940 -1.4020 0.9240 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5692 -1.3385 -0.1366 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0200 0.0417 -0.4251 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3798 0.7007 -1.2235 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1998 0.7009 0.1778 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1638 1.1782 -0.9029 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5826 -0.0741 -1.6768 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4034 1.6761 -0.2581 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4881 1.6671 0.9921 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4850 2.1553 -0.9615 O 0 0 0 0 0 0 0 0 0 0 0 0 9.6667 2.6267 -0.2938 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2799 -0.5856 0.6141 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3634 -0.4996 1.8347 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3885 -1.7701 1.6929 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5288 -2.5833 2.5640 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8620 -1.7139 0.2627 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3344 -1.1338 -0.4250 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0596 -0.0230 -1.3937 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3164 0.4503 -1.4916 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5430 1.2441 -2.4543 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3652 0.0569 -0.5673 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0991 -0.9488 0.2197 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1651 -1.3387 1.1618 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9655 -1.8701 2.2690 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6120 -1.1084 0.8285 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8182 -0.0505 -0.1790 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6453 0.7882 -0.5500 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9823 1.3732 -1.9324 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4820 1.5950 -2.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1783 1.8165 -0.8065 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8590 2.7851 -0.5632 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0156 0.7707 0.2337 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2276 -0.1612 0.0807 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9917 1.2747 1.6276 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4202 1.9947 0.3389 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9215 -2.2464 -1.2702 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1627 -3.1498 -0.0998 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7429 -1.1261 3.0812 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3326 0.2997 2.0532 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2270 -1.2384 2.1389 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3435 -2.4367 1.1888 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4789 -1.8138 0.3963 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4058 -1.9382 -1.0266 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7638 0.1058 0.8887 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8067 1.6009 0.7398 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6607 1.9118 -1.5348 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7597 -0.8503 -0.8753 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5590 0.1485 -2.1327 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8115 -0.3985 -2.3820 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4221 3.5469 0.2576 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0043 1.8401 0.4286 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4287 2.7729 -1.0882 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6095 0.4538 0.4251 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8811 -0.3576 2.7744 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3384 0.3328 1.6438 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6639 0.9015 -1.1395 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4034 -0.2415 -2.4442 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1924 -0.9031 1.7727 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9914 -2.1203 0.4956 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1529 -0.5695 -1.1304 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5305 2.3734 -2.0808 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7318 0.6410 -2.7418 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9756 0.6922 -2.5491 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6968 2.4518 -2.7552 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0209 -0.9861 -0.6103 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4964 -0.6025 1.0724 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1034 0.3982 -0.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7710 0.7549 2.2616 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0500 1.1403 2.1742 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3223 2.3560 1.6790 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2774 2.6423 0.4709 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8943 1.7110 1.2931 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6494 2.6197 -0.2055 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4120 -3.0431 -0.7419 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0047 -2.7406 -1.7288 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4322 -1.8546 -2.1870 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8083 -3.2617 -0.9954 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3100 -3.8292 -0.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8409 -3.5112 0.7408 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 2 0 4 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 2 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 24 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 2 0 31 33 1 0 33 34 1 0 33 35 1 0 28 36 1 0 18 37 1 0 17 38 1 0 18 13 1 0 23 17 1 0 28 22 1 0 33 27 1 0 1 39 1 0 1 40 1 0 1 41 1 0 2 42 1 0 3 43 1 0 3 44 1 0 6 45 1 0 6 46 1 0 7 47 1 0 8 48 1 0 8 49 1 0 8 50 1 0 12 51 1 0 12 52 1 0 12 53 1 0 13 54 1 0 14 55 1 0 14 56 1 0 19 57 1 0 19 58 1 0 26 59 1 0 26 60 1 0 27 61 1 0 29 62 1 0 29 63 1 0 30 64 1 0 30 65 1 0 34 66 1 0 34 67 1 0 34 68 1 0 35 69 1 0 35 70 1 0 35 71 1 0 36 72 1 0 36 73 1 0 36 74 1 0 37 75 1 0 37 76 1 0 37 77 1 0 38 78 1 0 38 79 1 0 38 80 1 0 M END

Standard InCHIKey	PLCLICIRIHEOIB-YFGNPAJLSA-N
Standard InCHI	InChI=1S/C31H42O7/c1-16(11-18(32)12-17(2)27(37)38-8)19-13-24(36)31(7)26-20(33)14-22-28(3,4)23(35)9-10-29(22,5)25(26)21(34)15-30(19,31)6/h16-17,19,22H,9-15H2,1-8H3/t16-,17?,19-,22+,29+,30-,31+/m1/s1
SMILES	CC(CC(=O)CC(C)C(=O)OC)C1CC(=O)C2(C1(CC(=O)C3=C2C(=O)CC4C3(CCC(=O)C4(C)C)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	526.29	Volume:	553.583 ? Van der Waals volume.
Dense:	0.951	LogP:	1.677 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.064 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.188 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	26.0
TPSA:	111.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.464	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.022	Fsp³:	0.742
MCE-18:	86.667 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.216	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.089 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.355 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.379	Promiscuous compounds:	0.043

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.923	MDCK Permeability:	-4.8
Pgp-inhibitor:	0.903	Pgp-substrate:	0.0
PAMPA:	0.12 ? 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%):	0.0	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.538

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.999
Plasma Protein Binding (PPB):	81.723%	Volume Distribution (VD):	0.27
Fu:	23.27% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.15
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.029
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.992
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

8.199

Half-life (T1/2):

0.285

ADMET: Toxicity

hERG Blockers:	0.022	hERG Blockers (10um):	0.178
Human Hepatotoxicity (H-HT):	0.562	Drug-induced Liver Injury (DILI):	0.143
AMES Toxicity:	0.112	Rat Oral Acute Toxicity:	0.31
Maximum Recommended Daily Dose:	0.807	Skin Sensitization:	0.332
Carcinogencity:	0.453	Eye Corrosion:	0.0
Eye Irritation:	0.024	Respiratory Toxicity:	0.103
Drug-induced Neurotoxicity:	0.78	Ototoxicity:	0.587
Hematotoxicity:	0.647	Drug-induced Nephrotoxicity:	0.648
Genotoxicity:	0.941	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.014	Hek293 Cytotoxicity:	0.181
BCF:	0.562 ? 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:	3.233 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.816 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.154 ? 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
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.phytochem.2005.10.025]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[11520245]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12045343]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14695801]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1791484]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	spore	n.a.	PMID[18827358]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	Nagano, Japan	2008-MAY	PMID[20039640]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20384295]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	n.a.	n.a.	PMID[20702092]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting bodies	n.a.	n.a.	PMID[21924611]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22014750]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[22044278]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	fruiting body	n.a.	n.a.	PMID[22047696]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26222905]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	fruit body	n.a.	PMID[9635497]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25269	Ganoderma lucidum	Species	Ganodermataceae	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
Inhibition	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
NPT520	Cell line	3T3-L1	Mus musculus	Inhibition	=	22.0	%	PMID[12444676]

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 NPC469561 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	25754
0.1-0.2	22894
0.2-0.3	1060
0.3-0.4	84
0.4-0.5	41
0.5-0.6	11
0.6-0.7	7
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	Natural Product ID
0.746	Intermediate Similarity	NPC106557
0.7458	Intermediate Similarity	NPC480122
0.7368	Intermediate Similarity	NPC271784
0.7143	Intermediate Similarity	NPC125622
0.6984	Remote Similarity	NPC112753
0.6613	Remote Similarity	NPC209882
0.6613	Remote Similarity	NPC607131
0.6557	Remote Similarity	NPC249212
0.6406	Remote Similarity	NPC480123
0.6087	Remote Similarity	NPC205899
0.6029	Remote Similarity	NPC600112
0.597	Remote Similarity	NPC470254
0.5942	Remote Similarity	NPC144660
0.5915	Remote Similarity	NPC119493
0.5806	Remote Similarity	NPC473039
0.5588	Remote Similarity	NPC3772
0.5429	Remote Similarity	NPC607625
0.5323	Remote Similarity	NPC473038
0.5217	Remote Similarity	NPC216904
0.5195	Remote Similarity	NPC56498
0.5139	Remote Similarity	NPC135854
0.5065	Remote Similarity	NPC281702

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC469561 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7486
0.1-0.2	1613
0.2-0.3	51
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