NPASS Compound

Natural Product: NPC536725

Natural Product ID	NPC536725
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 109114 0 0 0 0 0 0 0 0999 V2000 0.0423 -8.2524 0.2165 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9811 -7.3398 0.7372 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6963 -5.9781 0.7710 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5050 -5.5083 0.2889 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7778 -4.1576 0.3270 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1212 -3.2101 0.8419 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3205 -1.8266 0.8784 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5393 -0.7832 1.0741 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8671 -0.8983 1.2348 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8842 -0.9702 0.2443 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0115 -1.4566 0.7891 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1967 -1.0889 0.1995 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8515 -0.0423 1.0547 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0545 0.4098 0.5098 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6151 1.3916 1.3262 C 0 0 2 0 0 0 0 0 0 0 0 0 7.6605 2.5498 0.5695 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6827 2.6514 -0.3211 C 0 0 1 0 0 0 0 0 0 0 0 0 9.5081 3.9190 -0.0806 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5383 1.4619 -0.5422 C 0 0 2 0 0 0 0 0 0 0 0 0 9.1694 0.7671 -1.7202 O 0 0 0 0 0 0 0 0 0 0 0 0 9.7480 0.5216 0.5736 C 0 0 1 0 0 0 0 0 0 0 0 0 11.0963 0.2902 0.8602 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9622 0.9027 1.7775 C 0 0 2 0 0 0 0 0 0 0 0 0 8.7562 -0.2230 2.5825 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0614 -0.6439 -1.2106 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2974 -0.3018 -1.7863 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1809 0.5350 -1.3303 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8114 1.7715 -1.1795 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9878 0.3940 -0.4149 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8107 0.5575 -1.2108 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0571 0.4848 1.0931 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6022 1.5256 1.2755 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4172 0.6436 0.9150 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0124 1.8836 0.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1951 2.9905 1.1257 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3824 2.0165 0.7337 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2074 0.9229 0.5304 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5619 1.0518 0.3406 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2492 2.2454 0.3728 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2675 2.1121 1.3257 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5128 2.4932 0.8554 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.4368 2.4778 2.0675 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7265 2.8323 1.7633 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3808 3.8986 0.3098 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.6228 4.4671 0.1108 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6185 3.8154 -0.9947 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.5548 3.8142 -2.0327 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8434 2.5157 -1.0051 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7712 2.6809 -1.8861 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5949 -0.3282 0.5257 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4275 -1.5388 0.3181 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8209 -1.7012 -1.0954 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0621 -1.8362 -1.4590 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1764 -1.8412 -0.4886 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3863 -1.9906 -2.9190 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2147 -0.4522 0.7163 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6370 -1.6133 0.7097 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2995 -3.7052 1.3122 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5927 -5.0697 1.2807 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4249 -9.3015 0.2687 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8624 -8.2546 0.8766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2182 -8.0084 -0.8286 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2008 -6.2322 -0.1097 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7351 -3.8574 -0.0694 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4958 -1.6689 -0.5701 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8744 -1.9873 0.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1833 0.8384 1.1007 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9711 -0.3891 2.1002 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9729 1.5572 2.2389 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1708 2.8623 -1.3159 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8743 4.5958 0.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6860 4.4756 -1.0222 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4884 3.6920 0.3595 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5686 1.8684 -0.8193 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5465 1.2728 -2.2741 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3583 -0.4889 0.2496 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2480 0.3095 1.8558 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4813 1.6346 2.4340 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2756 0.0227 3.4309 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6728 -1.4610 -1.8820 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7363 -1.0408 -2.2468 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8026 0.5341 -2.4080 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3693 2.4332 -1.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0212 1.2411 0.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6238 -0.3251 -1.6515 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2855 3.5996 1.9291 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7362 3.0356 0.7579 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6324 3.1056 0.6193 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8856 1.8460 0.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3975 1.4178 2.4387 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0328 3.1033 2.8892 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.3948 2.3945 2.3528 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8142 4.4778 1.1006 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6452 5.3601 0.5761 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9482 4.6914 -1.1288 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4835 3.0064 -2.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4363 1.6526 -1.3540 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5554 3.6483 -1.9721 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8184 -2.4309 0.5899 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3028 -1.4978 0.9981 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0390 -1.7099 -1.8542 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1104 -2.2717 -0.9755 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4109 -0.8490 -0.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8990 -2.5194 0.3633 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0431 -1.0897 -3.4729 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9030 -2.9037 -3.3377 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4775 -2.1311 -3.0534 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0118 -3.0465 1.7568 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5249 -5.4499 1.6506 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 12 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 8 31 1 0 31 32 2 0 31 33 1 0 33 34 2 0 34 35 1 0 34 36 1 0 36 37 2 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 41 44 1 0 44 45 1 0 44 46 1 0 46 47 1 0 46 48 1 0 48 49 1 0 37 50 1 0 50 51 1 0 51 52 1 0 52 53 2 3 53 54 1 0 53 55 1 0 50 56 2 0 56 57 1 0 6 58 1 0 58 59 2 0 59 3 1 0 57 7 1 0 29 10 1 0 56 33 1 0 23 15 1 0 48 39 1 0 1 60 1 0 1 61 1 0 1 62 1 0 4 63 1 0 5 64 1 0 10 65 1 6 12 66 1 6 13 67 1 0 13 68 1 0 15 69 1 1 17 70 1 6 18 71 1 0 18 72 1 0 18 73 1 0 19 74 1 6 20 75 1 0 21 76 1 6 22 77 1 0 23 78 1 1 24 79 1 0 25 80 1 6 26 81 1 0 27 82 1 6 28 83 1 0 29 84 1 1 30 85 1 0 35 86 1 0 36 87 1 0 39 88 1 1 41 89 1 6 42 90 1 0 42 91 1 0 43 92 1 0 44 93 1 1 45 94 1 0 46 95 1 6 47 96 1 0 48 97 1 6 49 98 1 0 51 99 1 0 51100 1 0 52101 1 0 54102 1 0 54103 1 0 54104 1 0 55105 1 0 55106 1 0 55107 1 0 58108 1 0 59109 1 0 M END

Standard InCHIKey	SFPBPCAQVDGNMT-IATKZNDZSA-N
Standard InCHI	InChI=1S/C39H50O20/c1-14(2)5-10-18-20(55-38-32(50)29(47)25(43)21(12-40)56-38)11-19(41)23-27(45)36(34(58-35(18)23)16-6-8-17(52-4)9-7-16)59-39-33(51)30(48)26(44)22(57-39)13-53-37-31(49)28(46)24(42)15(3)54-37/h5-9,11,15,21-22,24-26,28-33,37-44,46-51H,10,12-13H2,1-4H3/t15-,21-,22+,24-,25-,26-,28+,29-,30-,31-,32+,33+,37+,38+,39-/m0/s1
SMILES	COC1=CC=C(C2=C(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]4O)[C@H](O)[C@H](O)[C@H]3O)C(=O)C3=C(O)C=C(O[C@@H]4O[C@@H](CO)[C@H](O)[C@H](O)[C@H]4O)C(CC=C(C)C)=C3O2)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	838.29	Volume:	783.838 ? Van der Waals volume.
Dense:	1.069	LogP:	1.456 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.061 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.728 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	37.0
TPSA:	317.35 ? Topological Polar Surface Area.	H-Bond Acceptor:	20.0
H-Bond Donor:	11.0	Rings:	6.0
Heavy Atoms:	20.0

MedChem Properties

QED Drug-Likeness Score:	0.087	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.558	Fsp³:	0.564
MCE-18:	153.639 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.682	Fluc inhibitor:	0.279 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.671 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.451 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.035	Promiscuous compounds:	0.153

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.529	MDCK Permeability:	-5.225
Pgp-inhibitor:	0.0	Pgp-substrate:	0.956
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):	1.0
20% Bioavailability (F20%):	0.986	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.148
Plasma Protein Binding (PPB):	78.036%	Volume Distribution (VD):	-0.033
Fu:	21.026% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.036
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.838
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

0.685

Half-life (T1/2):

3.234

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.041
Human Hepatotoxicity (H-HT):	0.75	Drug-induced Liver Injury (DILI):	0.997
AMES Toxicity:	0.995	Rat Oral Acute Toxicity:	0.012
Maximum Recommended Daily Dose:	0.003	Skin Sensitization:	1.0
Carcinogencity:	0.03	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.992
Hematotoxicity:	0.671	Drug-induced Nephrotoxicity:	0.985
Genotoxicity:	0.957	RPMI-8226 Immunitoxicity:	0.398
A549 Cytotoxicity:	0.97	Hek293 Cytotoxicity:	0.581
BCF:	0.665 ? 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:	3.517 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.409 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.436 ? 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
NPO21776	Sesbania grandiflora	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21776	Sesbania grandiflora	Species	Fabaceae	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

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

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 NPC536725 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	12684
0.1-0.2	31509
0.2-0.3	4509
0.3-0.4	813
0.4-0.5	277
0.5-0.6	57
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8511	High Similarity	NPC5319
0.6832	Remote Similarity	NPC131745
0.6275	Remote Similarity	NPC278419
0.6275	Remote Similarity	NPC179198
0.5888	Remote Similarity	NPC186816
0.5826	Remote Similarity	NPC25523
0.5794	Remote Similarity	NPC22062
0.5794	Remote Similarity	NPC473634
0.5794	Remote Similarity	NPC138811
0.5727	Remote Similarity	NPC473327
0.569	Remote Similarity	NPC480441
0.5641	Remote Similarity	NPC277532
0.5596	Remote Similarity	NPC473571
0.5596	Remote Similarity	NPC110941
0.5556	Remote Similarity	NPC173582
0.5556	Remote Similarity	NPC265885
0.5556	Remote Similarity	NPC181465
0.5556	Remote Similarity	NPC215710
0.5556	Remote Similarity	NPC473438
0.5556	Remote Similarity	NPC253788
0.5455	Remote Similarity	NPC204693
0.5405	Remote Similarity	NPC488073
0.5405	Remote Similarity	NPC126784
0.5405	Remote Similarity	NPC241423
0.5392	Remote Similarity	NPC289667
0.5391	Remote Similarity	NPC135358
0.5385	Remote Similarity	NPC472459
0.5364	Remote Similarity	NPC203259
0.5364	Remote Similarity	NPC65563
0.5364	Remote Similarity	NPC33054
0.5364	Remote Similarity	NPC470949
0.5364	Remote Similarity	NPC176740
0.5364	Remote Similarity	NPC471725
0.5364	Remote Similarity	NPC134532
0.5364	Remote Similarity	NPC156869
0.5364	Remote Similarity	NPC602582
0.5357	Remote Similarity	NPC470443
0.5351	Remote Similarity	NPC476472
0.5351	Remote Similarity	NPC294815
0.5351	Remote Similarity	NPC16194
0.5327	Remote Similarity	NPC66087
0.531	Remote Similarity	NPC209296
0.5273	Remote Similarity	NPC39834
0.5263	Remote Similarity	NPC142142
0.5254	Remote Similarity	NPC189564
0.5234	Remote Similarity	NPC116458
0.5234	Remote Similarity	NPC246943
0.5229	Remote Similarity	NPC251417
0.5194	Remote Similarity	NPC483159
0.5194	Remote Similarity	NPC483160
0.5182	Remote Similarity	NPC187379
0.5169	Remote Similarity	NPC203145
0.5128	Remote Similarity	NPC602448
0.5124	Remote Similarity	NPC311850
0.5093	Remote Similarity	NPC605784
0.5089	Remote Similarity	NPC475155
0.5085	Remote Similarity	NPC14187
0.5083	Remote Similarity	NPC292019
0.5083	Remote Similarity	NPC202908
0.5048	Remote Similarity	NPC64305
0.5045	Remote Similarity	NPC480466

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC536725 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3743
0.1-0.2	5313
0.2-0.3	80
0.3-0.4	8
0.4-0.5	1
0.5-0.6	4
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8511	High Similarity	NPD7804	Clinical (unspecified phase)
0.5702	Remote Similarity	NPD7808	Phase 3
0.5625	Remote Similarity	NPD7251	Phase 2
0.5364	Remote Similarity	NPD6797	Phase 2
0.531	Remote Similarity	NPD7054	Phase 4

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