NPASS Compound

Natural Product: NPC212948

Natural Product ID	NPC212948
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ganoderic Acid Y
IUPAC Name	(E,6R)-6-[(3S,5R,10S,13R,14R,17R)-3-hydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methylhept-2-enoic acid
Synonyms	Ganoderic Acid Y
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1915760
PubChem CID	57397445
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 79 82 0 0 0 0 0 0 0 0999 V2000 3.6671 0.9207 0.5933 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3363 -0.1469 -0.4102 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0626 0.1316 -1.1413 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7627 -0.9242 -2.1916 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2864 -1.1885 -2.1669 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2366 -0.0501 -1.3517 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8231 0.0656 -0.2743 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8323 -1.2026 0.5519 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5276 1.2327 0.5718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8959 1.1678 1.0517 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8406 0.4429 0.4853 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5179 -0.3541 -0.6813 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3376 -1.3068 -1.1062 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6257 -1.5610 -0.3806 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1191 -0.1773 0.0049 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2278 0.4057 1.0323 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1337 -0.3883 2.3084 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6600 1.8104 1.3630 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1120 1.9559 1.5963 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9543 0.7376 1.4487 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5831 -0.1293 0.2929 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3525 0.4307 -0.9199 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1907 -1.5150 0.4980 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0864 0.0447 2.6506 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3796 1.1856 -2.1800 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5127 -0.5094 -1.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6246 -1.1176 -0.4355 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2334 -0.4017 0.6517 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4942 0.0040 0.5924 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0709 0.7194 1.7016 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2650 1.1231 1.6878 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3460 1.0112 2.8621 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3226 -0.2681 -0.6021 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5043 0.6312 1.6286 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6601 1.4014 0.3766 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9807 1.8286 0.4307 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1683 -1.0820 0.2664 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1034 1.1101 -1.6224 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0077 -0.5437 -3.2175 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3629 -1.8439 -2.0620 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1586 -1.2440 -3.1817 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0769 -2.1599 -1.6735 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3746 -2.0273 0.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1915 -1.5820 0.7472 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2664 -0.9433 1.5416 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6801 2.1767 0.0182 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1052 1.2344 1.5454 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1821 1.7481 1.9168 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0617 -1.8783 -1.9634 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5463 -2.2622 0.4378 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3331 -1.9601 -1.1325 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9549 0.4324 -0.9355 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0792 -0.7201 2.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7228 -1.3026 2.3243 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4058 0.2503 3.1726 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1407 2.0706 2.3329 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2351 2.5307 0.6224 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3477 2.3788 2.6187 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4676 2.7819 0.9074 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0075 1.1070 1.2571 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3408 -0.3104 -1.7421 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8058 1.3269 -1.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3791 0.7105 -0.6387 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5564 -2.1896 1.0600 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2849 -1.9533 -0.5353 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1981 -1.3720 0.8857 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1174 -0.9200 2.5556 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3120 1.9965 -1.9643 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4565 1.5190 -2.1527 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2335 0.8863 -3.2600 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2768 -1.2919 -2.0123 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8475 0.4310 -1.7458 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4554 -1.4683 -1.1284 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2149 -2.1199 -0.0713 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7239 -0.1818 1.5787 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5975 1.7755 3.4553 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4538 -1.3865 -0.6488 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2846 0.2402 -0.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8358 0.0265 -1.5423 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 1 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 1 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 20 24 1 0 6 25 1 6 2 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 29 33 1 0 7 3 1 0 16 11 1 0 12 6 1 0 21 15 1 0 1 34 1 0 1 35 1 0 1 36 1 0 2 37 1 1 3 38 1 6 4 39 1 0 4 40 1 0 5 41 1 0 5 42 1 0 8 43 1 0 8 44 1 0 8 45 1 0 9 46 1 0 9 47 1 0 10 48 1 0 13 49 1 0 14 50 1 0 14 51 1 0 15 52 1 6 17 53 1 0 17 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 0 19 59 1 0 20 60 1 6 22 61 1 0 22 62 1 0 22 63 1 0 23 64 1 0 23 65 1 0 23 66 1 0 24 67 1 0 25 68 1 0 25 69 1 0 25 70 1 0 26 71 1 0 26 72 1 0 27 73 1 0 27 74 1 0 28 75 1 0 32 76 1 0 33 77 1 0 33 78 1 0 33 79 1 0 M END

Standard InCHIKey	HUTCYUJPLOTDMX-SPPZYOJVSA-N
Standard InCHI	InChI=1S/C30H46O3/c1-19(9-8-10-20(2)26(32)33)21-13-17-30(7)23-11-12-24-27(3,4)25(31)15-16-28(24,5)22(23)14-18-29(21,30)6/h10-11,14,19,21,24-25,31H,8-9,12-13,15-18H2,1-7H3,(H,32,33)/b20-10+/t19-,21-,24+,25+,28-,29-,30+/m1/s1
SMILES	C[C@@H]([C@H]1CC[C@@]2([C@]1(C)CC=C1C2=CC[C@@H]2[C@]1(C)CC[C@@H](C2(C)C)O)C)CC/C=C(/C(=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.34	Volume:	509.035 ? Van der Waals volume.
Dense:	0.893	LogP:	5.831 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.359 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.536 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	22.0
TPSA:	57.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.428	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.805	Fsp³:	0.767
MCE-18:	79.698 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.865	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.025 ? 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:	0.583	Promiscuous compounds:	0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.246	MDCK Permeability:	-4.922
Pgp-inhibitor:	0.145	Pgp-substrate:	0.007
PAMPA:	0.945 ? 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):	0.001
20% Bioavailability (F20%):	0.388	30% Bioavailability (F30%):	0.339
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.725
Plasma Protein Binding (PPB):	88.605%	Volume Distribution (VD):	-0.3
Fu:	9.089% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.516
BSEP inhibitor:	0.881

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.031
CYP2C19-inhibitor:	0.726	CYP2C19-substrate:	0.465
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.013
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.049
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.695 ? 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):

7.624

Half-life (T1/2):

0.748

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.061
Human Hepatotoxicity (H-HT):	0.675	Drug-induced Liver Injury (DILI):	0.239
AMES Toxicity:	0.106	Rat Oral Acute Toxicity:	0.141
Maximum Recommended Daily Dose:	0.488	Skin Sensitization:	0.914
Carcinogencity:	0.344	Eye Corrosion:	0.03
Eye Irritation:	0.736	Respiratory Toxicity:	0.792
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.694
Hematotoxicity:	0.259	Drug-induced Nephrotoxicity:	0.629
Genotoxicity:	0.468	RPMI-8226 Immunitoxicity:	0.063
A549 Cytotoxicity:	0.05	Hek293 Cytotoxicity:	0.154
BCF:	1.313 ? 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:	4.228 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.644 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.033 ? 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]
NPO33020	ganoderma leucocontextum	Species	Ganodermataceae	Eukaryota	fruiting bodies	Tibetan	n.a.	PMID[26287401]
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	8

Activity Type	# Activity
Individual protein	4
Cell line	3
Others	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	=	21110.0	nM	PMID[21924611]
NPT1088	Individual protein	3-hydroxy-3-methylglutaryl-coenzyme A reductase	Sus scrofa	IC50	=	8600.0	nM	PMID[26287401]
NPT204	Individual protein	Acetylcholinesterase	Homo sapiens	IC50	=	21100.0	nM	PMID[31035236]
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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	11000.0	nM	PMID[23092389]
NPT111	Cell line	K562	Homo sapiens	IC50	=	17500.0	nM	PMID[26287401]
NPT306	Cell line	PC-3	Homo sapiens	IC50	=	179800.0	nM	PMID[26287401]
NPT2	Others	Unspecified	n.a.	IC50	>	50000.0	nM	PMID[26287401]

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 NPC212948 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	21376
0.1-0.2	23858
0.2-0.3	3920
0.3-0.4	527
0.4-0.5	121
0.5-0.6	33
0.6-0.7	9
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
0.7812	Intermediate Similarity	NPC214697
0.7656	Intermediate Similarity	NPC138536
0.7627	Intermediate Similarity	NPC205455
0.7541	Intermediate Similarity	NPC202389
0.7313	Intermediate Similarity	NPC141401
0.7302	Intermediate Similarity	NPC475772
0.7101	Intermediate Similarity	NPC39082
0.7101	Intermediate Similarity	NPC610107
0.7059	Intermediate Similarity	NPC478313
0.7059	Intermediate Similarity	NPC489790
0.697	Remote Similarity	NPC87552
0.6935	Remote Similarity	NPC6707
0.6567	Remote Similarity	NPC84271
0.6567	Remote Similarity	NPC102414
0.6522	Remote Similarity	NPC469406
0.6377	Remote Similarity	NPC472240
0.6377	Remote Similarity	NPC262858
0.6286	Remote Similarity	NPC601194
0.6143	Remote Similarity	NPC77168
0.597	Remote Similarity	NPC231310
0.5921	Remote Similarity	NPC94393
0.5857	Remote Similarity	NPC222845
0.5857	Remote Similarity	NPC296577
0.5833	Remote Similarity	NPC48647
0.5811	Remote Similarity	NPC285702
0.5811	Remote Similarity	NPC166745
0.5811	Remote Similarity	NPC235464
0.5672	Remote Similarity	NPC147568
0.5606	Remote Similarity	NPC20853
0.56	Remote Similarity	NPC489791
0.56	Remote Similarity	NPC136044
0.56	Remote Similarity	NPC484797
0.5588	Remote Similarity	NPC110923
0.5588	Remote Similarity	NPC74296
0.5526	Remote Similarity	NPC58410
0.5479	Remote Similarity	NPC45324
0.5479	Remote Similarity	NPC162001
0.5467	Remote Similarity	NPC276127
0.5467	Remote Similarity	NPC478307
0.5405	Remote Similarity	NPC484975
0.5405	Remote Similarity	NPC186810
0.5405	Remote Similarity	NPC321301
0.5395	Remote Similarity	NPC478312
0.5385	Remote Similarity	NPC137552
0.5385	Remote Similarity	NPC99411
0.5373	Remote Similarity	NPC72507
0.5352	Remote Similarity	NPC4166
0.5263	Remote Similarity	NPC489801
0.5139	Remote Similarity	NPC89077
0.5139	Remote Similarity	NPC311092
0.5135	Remote Similarity	NPC146554
0.507	Remote Similarity	NPC201852

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC212948 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6564
0.1-0.2	2479
0.2-0.3	101
0.3-0.4	6
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