NPASS Compound

Natural Product: NPC115303

Natural Product ID	NPC115303
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ganoderic Acid K
IUPAC Name	(6R)-6-[(3S,5R,7S,10S,12S,13R,14R,17R)-12-acetyloxy-3,7-dihydroxy-4,4,10,13,14-pentamethyl-11,15-dioxo-2,3,5,6,7,12,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-methyl-4-oxoheptanoic acid
Synonyms	Ganoderic Acid K
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1922177
PubChem CID	57403756
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 87 90 0 0 0 0 0 0 0 0999 V2000 6.1936 -0.8943 -1.1090 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5506 -1.1633 -0.0628 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3317 -1.1356 1.1687 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9916 0.0285 2.0572 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8007 0.0658 3.2913 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6540 -0.8607 3.4602 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6725 1.0486 4.2482 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0723 1.3520 1.3401 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1074 -1.4566 -0.2353 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4045 -0.4927 -1.1141 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0178 -0.6308 -1.4427 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6680 -1.9553 -2.1454 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2437 -1.6715 -2.4853 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4633 -2.3044 -3.2632 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2117 -0.4803 -1.7318 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8485 -0.4932 -0.5900 C 0 0 1 0 0 0 0 0 0 0 0 0 0.4848 -1.7613 0.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6702 0.6847 0.2372 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3686 0.5765 1.4894 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0961 1.6243 2.0054 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1639 2.6862 1.3217 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7882 1.5438 3.3297 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8100 0.7387 0.6307 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0605 1.4100 1.6419 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8563 0.0745 -0.0908 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5855 -0.5379 -1.2674 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6192 -1.2036 -2.0649 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5857 -2.5674 -1.7907 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9919 -0.6172 -1.9023 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1009 0.4146 -0.8101 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2643 0.0092 0.3857 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5677 -1.4039 0.8337 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4861 0.9174 1.5570 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9662 1.0157 1.9061 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6150 1.6613 0.7027 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4829 0.8253 -0.5448 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9302 1.7469 -1.6881 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5049 -0.2694 -0.4383 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9659 1.8397 1.0004 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0176 0.7119 -2.6382 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1868 -0.2919 -2.4218 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1726 -2.0655 1.7443 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4400 -1.0703 0.9911 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9337 -0.0614 2.4274 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4879 1.3731 4.7588 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2188 1.2058 0.2265 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8856 1.9970 1.6703 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0817 1.9060 1.3807 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6637 -1.4408 0.7784 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0002 -2.5175 -0.5688 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5238 0.5227 -0.5990 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8530 0.1135 -2.3166 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2192 -2.1067 -3.0696 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7065 -2.8147 -1.4678 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1890 -1.5034 1.0019 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0254 -2.5113 -0.4543 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3629 -2.2527 0.6307 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9461 1.6484 -0.1921 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0330 0.5008 3.6255 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0138 1.8506 4.1045 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6628 2.1944 3.3980 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4045 -1.1202 -3.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3529 -2.9738 -2.2723 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3575 -0.1241 -2.8241 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6908 -1.4843 -1.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5706 1.3172 -1.2368 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3088 -1.9088 0.2099 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0020 -1.4231 1.8725 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6223 -1.9714 0.9285 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2062 1.9805 1.3299 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9964 0.4909 2.4419 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4015 0.0718 2.2112 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0467 1.7343 2.7438 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1680 2.6734 0.5881 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8959 2.1847 -1.3688 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2161 2.6050 -1.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0526 1.2001 -2.6208 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4414 -0.8716 0.4919 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5073 0.2574 -0.3734 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5931 -0.9210 -1.3153 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1434 2.0471 1.9458 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0573 1.0993 -2.8752 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4850 1.5695 -2.1632 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3702 0.4375 -3.6365 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4722 0.1174 -3.2118 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9514 0.4935 -2.3476 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5354 -1.2339 -2.8601 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 4 8 1 0 2 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 13 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 2 0 20 22 1 0 18 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 30 31 1 0 31 32 1 1 31 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 36 38 1 0 35 39 1 0 15 40 1 6 10 41 1 0 16 11 1 0 31 25 1 0 26 15 1 0 36 30 1 0 3 42 1 0 3 43 1 0 4 44 1 0 7 45 1 0 8 46 1 0 8 47 1 0 8 48 1 0 9 49 1 0 9 50 1 0 10 51 1 1 11 52 1 6 12 53 1 0 12 54 1 0 17 55 1 0 17 56 1 0 17 57 1 0 18 58 1 6 22 59 1 0 22 60 1 0 22 61 1 0 27 62 1 6 28 63 1 0 29 64 1 0 29 65 1 0 30 66 1 6 32 67 1 0 32 68 1 0 32 69 1 0 33 70 1 0 33 71 1 0 34 72 1 0 34 73 1 0 35 74 1 6 37 75 1 0 37 76 1 0 37 77 1 0 38 78 1 0 38 79 1 0 38 80 1 0 39 81 1 0 40 82 1 0 40 83 1 0 40 84 1 0 41 85 1 0 41 86 1 0 41 87 1 0 M END

Standard InCHIKey	OEHYQHPDUCRLMW-BHYSALSHSA-N
Standard InCHI	InChI=1S/C32H46O9/c1-15(11-18(34)12-16(2)28(39)40)19-13-23(37)32(8)24-20(35)14-21-29(4,5)22(36)9-10-30(21,6)25(24)26(38)27(31(19,32)7)41-17(3)33/h15-16,19-22,27,35-36H,9-14H2,1-8H3,(H,39,40)/t15-,16?,19-,20+,21+,22+,27-,30+,31+,32+/m1/s1
SMILES	O=C(CC(C(=O)O)C)C[C@H]([C@H]1CC(=O)[C@@]2([C@]1(C)[C@H](OC(=O)C)C(=O)C1=C2[C@@H](O)C[C@@H]2[C@]1(C)CC[C@@H](C2(C)C)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	574.31	Volume:	591.095 ? Van der Waals volume.
Dense:	0.972	LogP:	1.917 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.982 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.602 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	25.0
TPSA:	155.27 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.386	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.366	Fsp³:	0.781
MCE-18:	93.333 ? 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:	0.918	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.027 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.255	Promiscuous compounds:	0.26

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.429	MDCK Permeability:	-4.89
Pgp-inhibitor:	0.002	Pgp-substrate:	0.264
PAMPA:	1.0 ? 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%):	0.011	30% Bioavailability (F30%):	0.001
50% Bioavailability (F50%):	0.732

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.993
Plasma Protein Binding (PPB):	78.328%	Volume Distribution (VD):	-0.485
Fu:	21.625% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.84

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.071	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.949	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.055
HLM stability:	0.009 ? 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):

3.348

Half-life (T1/2):

1.912

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.019
Human Hepatotoxicity (H-HT):	0.519	Drug-induced Liver Injury (DILI):	0.474
AMES Toxicity:	0.075	Rat Oral Acute Toxicity:	0.293
Maximum Recommended Daily Dose:	0.759	Skin Sensitization:	0.868
Carcinogencity:	0.349	Eye Corrosion:	0.0
Eye Irritation:	0.133	Respiratory Toxicity:	0.297
Drug-induced Neurotoxicity:	0.051	Ototoxicity:	0.736
Hematotoxicity:	0.448	Drug-induced Nephrotoxicity:	0.93
Genotoxicity:	0.93	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.008	Hek293 Cytotoxicity:	0.026
BCF:	0.338 ? 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:	3.014 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.52 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.56 ? 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	7

Activity Type	# Activity
Individual protein	1
Cell line	4
Others	1
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT41	Individual protein	Aldose reductase	Homo sapiens	IC50	>	174200.0	nM	PMID[22047696]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT515	Cell line	SGC-7901	Homo sapiens	IC50	=	7250.0	nM	PMID[23092389]
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	7250.0	nM	PMID[23092389]
NPT168	Cell line	P388	Mus musculus	IC50	=	7250.0	nM	PMID[23092389]
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	300000.0	nM	PMID[23092389]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	3650.0	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 NPC115303 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	17524
0.1-0.2	28523
0.2-0.3	3657
0.3-0.4	89
0.4-0.5	31
0.5-0.6	19
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC2436
0.7714	Intermediate Similarity	NPC286174
0.7465	Intermediate Similarity	NPC600026
0.7222	Intermediate Similarity	NPC51452
0.7123	Intermediate Similarity	NPC16021
0.7042	Intermediate Similarity	NPC77947
0.6494	Remote Similarity	NPC129689
0.6316	Remote Similarity	NPC53222
0.6133	Remote Similarity	NPC33973
0.6104	Remote Similarity	NPC55872
0.6098	Remote Similarity	NPC472927
0.6	Remote Similarity	NPC488422
0.6	Remote Similarity	NPC255809
0.5926	Remote Similarity	NPC604894
0.5921	Remote Similarity	NPC157787
0.5844	Remote Similarity	NPC135854
0.5584	Remote Similarity	NPC70967
0.5513	Remote Similarity	NPC251017
0.55	Remote Similarity	NPC243525
0.55	Remote Similarity	NPC40765
0.5443	Remote Similarity	NPC122294
0.5422	Remote Similarity	NPC470251
0.5385	Remote Similarity	NPC488420
0.5385	Remote Similarity	NPC600686
0.5375	Remote Similarity	NPC144660
0.5301	Remote Similarity	NPC21358
0.5301	Remote Similarity	NPC234892
0.5125	Remote Similarity	NPC107690
0.5104	Remote Similarity	NPC472933
0.506	Remote Similarity	NPC216245
0.506	Remote Similarity	NPC95565
0.506	Remote Similarity	NPC609201

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC115303 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5795
0.1-0.2	3292
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