NPASS Compound

Natural Product: NPC205899

Natural Product ID	NPC205899
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl Ganoderate A
IUPAC Name	methyl (6R)-6-[(5R,7S,10S,13R,14R,15S,17R)-7,15-dihydroxy-4,4,10,13,14-pentamethyl-3,11-dioxo-2,5,6,7,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-4-oxoheptanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1086927
PubChem CID	21632954
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 84 87 0 0 0 0 0 0 0 0999 V2000 2.2863 -0.4834 -2.7873 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5683 -0.0952 -1.3124 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9582 -0.6454 -1.0948 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6057 -0.4759 0.1789 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5654 -1.3974 1.0151 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3425 0.7598 0.5684 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5755 0.9896 -0.2494 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2328 2.2621 0.2528 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5229 -0.1263 -0.0614 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9116 -0.8515 -1.0238 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0470 -0.4505 1.1796 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9603 -1.5290 1.3444 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6027 -0.7438 -0.4049 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8351 -0.3182 1.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5104 0.4260 1.3587 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4412 -0.4994 0.6986 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2967 -1.8505 1.3685 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8394 -0.0375 0.6085 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6048 -0.7254 -0.2461 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9232 -1.8218 -0.9497 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6092 -2.8666 -1.2261 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4963 -1.7554 -1.3401 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1455 -0.5600 -0.7103 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1941 0.6613 -1.5002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0421 -0.4344 -0.4920 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1989 0.0670 -1.9088 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8341 -1.7284 -0.3953 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2523 -1.5093 0.0972 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7137 -0.1434 -0.2120 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7032 0.0319 -0.8738 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9414 1.0023 0.3036 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0436 2.2352 -0.5392 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5522 1.3316 1.6738 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5281 0.5244 0.5345 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5614 1.6665 0.6934 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3269 1.0851 1.4031 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4222 2.0646 1.7075 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3376 0.4308 2.7380 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7219 0.3542 -3.2461 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8281 -1.4670 -2.8756 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2433 -0.5274 -3.3506 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5083 0.9999 -1.2241 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9493 -1.7391 -1.4025 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6720 -0.2117 -1.8753 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6324 0.7227 1.6323 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6462 1.6310 0.4793 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3079 1.0866 -1.3335 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4368 3.0546 0.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0985 2.5608 -0.3660 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5272 2.0776 1.3182 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8164 -2.3187 0.5861 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0072 -1.1454 1.1893 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9058 -1.9919 2.3325 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8011 -1.8708 -0.4884 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9536 -1.1731 1.7113 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5897 0.4358 1.1887 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6215 1.4116 0.9061 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4578 -2.5006 0.9192 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2744 -2.3699 1.3443 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1058 -1.6668 2.4641 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0262 -2.7194 -1.0462 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4908 -1.7439 -2.4480 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5446 1.4605 -1.4768 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5613 0.4017 -2.5374 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1183 1.1004 -1.0136 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3605 0.7624 -2.1445 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1880 0.4479 -2.1493 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0284 -0.8299 -2.5768 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8282 -2.2004 -1.4002 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3098 -2.4202 0.3007 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9464 -2.2737 -0.2954 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1911 -1.5877 1.2242 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8450 2.1444 -1.3277 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0626 2.5320 -0.9761 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3563 3.1269 0.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2051 2.3358 1.9916 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6488 1.3722 1.6070 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2440 0.6108 2.4372 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5349 -0.0131 1.5122 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0086 2.4887 1.3017 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1961 2.0577 -0.2979 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6887 0.6489 2.3817 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6004 2.5190 2.5652 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0674 -0.0625 3.1431 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 1 0 16 17 1 1 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 23 24 1 6 19 25 1 0 25 26 1 6 25 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 1 0 31 33 1 0 31 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 15 38 1 0 23 13 1 0 34 25 1 0 23 16 1 0 36 18 1 0 1 39 1 0 1 40 1 0 1 41 1 0 2 42 1 6 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 1 14 55 1 0 14 56 1 0 15 57 1 6 17 58 1 0 17 59 1 0 17 60 1 0 22 61 1 0 22 62 1 0 24 63 1 0 24 64 1 0 24 65 1 0 26 66 1 0 26 67 1 0 26 68 1 0 27 69 1 0 27 70 1 0 28 71 1 0 28 72 1 0 32 73 1 0 32 74 1 0 32 75 1 0 33 76 1 0 33 77 1 0 33 78 1 0 34 79 1 1 35 80 1 0 35 81 1 0 36 82 1 1 37 83 1 0 38 84 1 0 M END

Standard InCHIKey	GBFBBVYGZAABTI-LEEGDDNGSA-N
Standard InCHI	InChI=1S/C31H46O7/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/h16-17,19-20,22,24,33,36H,9-15H2,1-8H3/t16-,17?,19-,20+,22+,24+,29+,30-,31+/m1/s1
SMILES	C[C@H](CC(=O)CC(C)C(=O)OC)[C@H]1C[C@@H]([C@@]2(C)C3=C(C(=O)C[C@]12C)[C@@]1(C)CCC(=O)C(C)(C)[C@@H]1C[C@@H]3O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	530.32	Volume:	558.855 ? Van der Waals volume.
Dense:	0.949	LogP:	2.008 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.223 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.696 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	117.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.494	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.184	Fsp³:	0.806
MCE-18:	88.714 ? 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:	0.963	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.016 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.31	Promiscuous compounds:	0.479

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.166	MDCK Permeability:	-4.773
Pgp-inhibitor:	0.155	Pgp-substrate:	0.162
PAMPA:	0.984 ? 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%):	0.012	30% Bioavailability (F30%):	0.032
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.997
Plasma Protein Binding (PPB):	71.186%	Volume Distribution (VD):	0.016
Fu:	34.892% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.003
BSEP inhibitor:	0.993

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.22
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.467
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.998
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.997
HLM stability:	0.921 ? 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):

8.963

Half-life (T1/2):

0.675

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.075
Human Hepatotoxicity (H-HT):	0.697	Drug-induced Liver Injury (DILI):	0.39
AMES Toxicity:	0.334	Rat Oral Acute Toxicity:	0.739
Maximum Recommended Daily Dose:	0.748	Skin Sensitization:	0.997
Carcinogencity:	0.912	Eye Corrosion:	0.001
Eye Irritation:	0.187	Respiratory Toxicity:	0.697
Drug-induced Neurotoxicity:	0.473	Ototoxicity:	0.648
Hematotoxicity:	0.916	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.124
A549 Cytotoxicity:	0.158	Hek293 Cytotoxicity:	0.191
BCF:	0.496 ? 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:	3.146 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.665 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.877 ? 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]
NPO16609	Ganoderma sinense	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]
NPO16609	Ganoderma sinense	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[TM-MC]
NPO16609	Ganoderma sinense	Species	Ganodermataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
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
IC50	5
Inhibition	1

Activity Type	# Activity
Individual protein	3
Cell line	1
Others	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	IC50	=	30260.0	nM	PMID[21924611]
NPT41	Individual protein	Aldose reductase	Homo sapiens	IC50	>	189400.0	nM	PMID[22047696]
NPT439	Individual protein	Butyrylcholinesterase	Homo sapiens	IC50	>	200000.0	nM	PMID[21924611]

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[20039640]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	8010.0	nM	PMID[27335254]
NPT2	Others	Unspecified	n.a.	IC50	>	600000.0	nM	PMID[24070782]

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 NPC205899 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	20185
0.1-0.2	27492
0.2-0.3	1992
0.3-0.4	113
0.4-0.5	33
0.5-0.6	29
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8261	Intermediate Similarity	NPC56498
0.8	Intermediate Similarity	NPC125622
0.7879	Intermediate Similarity	NPC28656
0.7761	Intermediate Similarity	NPC106557
0.7692	Intermediate Similarity	NPC18319
0.7246	Intermediate Similarity	NPC10364
0.7143	Intermediate Similarity	NPC236390
0.7042	Intermediate Similarity	NPC606047
0.6338	Remote Similarity	NPC470254
0.6301	Remote Similarity	NPC144660
0.6087	Remote Similarity	NPC469561
0.5972	Remote Similarity	NPC3772
0.5729	Remote Similarity	NPC600997
0.5729	Remote Similarity	NPC601439
0.5584	Remote Similarity	NPC55872
0.5526	Remote Similarity	NPC241156
0.5526	Remote Similarity	NPC488419
0.5526	Remote Similarity	NPC600288
0.5385	Remote Similarity	NPC243525
0.5385	Remote Similarity	NPC40765
0.5385	Remote Similarity	NPC600080
0.5362	Remote Similarity	NPC611512
0.5326	Remote Similarity	NPC611554
0.5325	Remote Similarity	NPC264404
0.525	Remote Similarity	NPC25750
0.525	Remote Similarity	NPC119493
0.525	Remote Similarity	NPC610087
0.5244	Remote Similarity	NPC281702
0.519	Remote Similarity	NPC204450
0.519	Remote Similarity	NPC184870
0.519	Remote Similarity	NPC195290
0.5155	Remote Similarity	NPC604793
0.5135	Remote Similarity	NPC480122
0.5125	Remote Similarity	NPC121339
0.5104	Remote Similarity	NPC604929
0.5102	Remote Similarity	NPC603740
0.5102	Remote Similarity	NPC607298
0.5063	Remote Similarity	NPC488423
0.5051	Remote Similarity	NPC488417
0.5051	Remote Similarity	NPC610721

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC205899 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7144
0.1-0.2	1943
0.2-0.3	63
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