NPASS Compound

Natural Product: NPC480076

Natural Product ID	NPC480076
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NPGCUMNTYUYRCR-RWIDSCNISA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44584452
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 111113 0 0 0 0 0 0 0 0999 V2000 -12.7115 -2.2005 -1.4909 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.5245 -1.5451 -0.7294 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5014 -1.2103 -1.7520 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2318 -0.5964 -1.3064 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2144 0.7017 -0.6418 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9142 0.9400 0.6332 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5606 0.0703 1.7729 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1081 0.0798 2.2142 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7085 1.4290 2.6267 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3542 1.6133 3.1439 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1787 1.4628 2.3134 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8895 0.1743 1.6528 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2809 0.1630 0.1778 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9622 0.1275 -0.5508 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0172 0.6181 0.4813 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5940 0.1199 0.2574 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9510 0.8240 -0.9097 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5003 0.5023 -0.6386 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5186 0.2586 0.8422 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8486 -1.1061 1.2817 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1097 -1.7567 0.9089 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4039 -1.1977 1.2913 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8931 0.0886 0.7944 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0847 0.1675 -0.7048 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1201 -0.8557 -1.1217 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3871 -0.9118 -2.5810 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8579 0.3321 -3.2319 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1462 0.8702 -2.6868 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2686 -0.1104 -2.8255 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5794 0.4456 -2.3201 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5402 0.8285 -0.8869 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2391 -0.2692 0.0754 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0732 0.0144 1.3224 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0977 -1.0964 1.4904 C 0 0 0 0 0 0 0 0 0 0 0 0 12.0017 -1.1772 0.3164 C 0 0 0 0 0 0 0 0 0 0 0 0 11.7501 -1.8585 -0.6645 O 0 0 0 0 0 0 0 0 0 0 0 0 13.2999 -0.4110 0.2687 C 0 0 0 0 0 0 0 0 0 0 0 0 10.7467 1.2912 0.9833 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1901 2.1899 1.7751 O 0 0 0 0 0 0 0 0 0 0 0 0 10.8058 1.3247 -0.4246 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7702 -1.1750 2.7120 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8007 0.5078 1.3166 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4825 0.0460 1.6306 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8061 2.5815 1.5365 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4574 -0.4337 -2.5119 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.2898 -1.3538 -1.9279 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.3312 -2.7639 -0.7949 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.2818 -2.8197 -2.2848 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1255 -2.2982 0.0061 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9595 -0.7289 -0.1750 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2852 -2.1594 -2.3453 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9633 -0.5534 -2.5680 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5879 -1.3644 -0.7560 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1509 1.0783 -0.5738 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6673 1.4530 -1.3854 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0105 1.0667 0.5592 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6023 2.0016 0.9534 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1541 0.4298 2.6646 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9160 -0.9919 1.6455 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4834 -0.5084 1.5659 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1404 -0.5392 3.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8952 2.2093 1.8144 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4361 1.7696 3.4250 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1934 0.9081 4.0660 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2857 2.6212 3.7123 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2927 1.5633 3.1535 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2406 -0.7234 2.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8397 -0.7602 -0.0206 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8554 1.0861 -0.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7634 -0.9160 -0.8827 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0484 0.7993 -1.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0232 1.7303 0.4613 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6091 -0.9465 0.0536 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0784 1.9115 -0.8743 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2669 0.4166 -1.8848 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1646 1.3487 -0.9543 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7530 -0.4401 -1.1676 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1706 1.0546 1.2698 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0126 -1.7995 0.9267 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0312 -2.0316 -0.1805 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0660 -2.7959 1.3916 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2181 -1.9846 1.1547 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3921 -1.1132 2.4344 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4567 0.9970 1.2369 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9819 0.1603 1.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1920 0.1418 -1.3071 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5650 1.1764 -0.8888 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7341 -1.8570 -0.7970 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0740 -0.7288 -0.5800 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4901 -1.3301 -3.1243 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1679 -1.6958 -2.7381 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0775 1.1279 -3.2797 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0837 0.0566 -4.3098 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4100 1.7828 -3.2874 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9708 1.1519 -1.6147 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0423 -0.9972 -2.1693 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3979 -0.4575 -3.8524 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3483 -0.3661 -2.4788 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9469 1.2802 -2.9614 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8304 1.6624 -0.6802 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1817 -0.2534 0.3982 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4325 -1.2887 -0.3008 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4343 0.1094 2.2249 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6758 -0.8775 2.4245 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5945 -2.0709 1.6488 H 0 0 0 0 0 0 0 0 0 0 0 0 14.1127 -1.1065 0.5280 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2863 0.4012 1.0118 H 0 0 0 0 0 0 0 0 0 0 0 0 13.4815 -0.0658 -0.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1346 -0.8233 2.9757 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6125 3.3565 2.1226 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2358 -1.3488 -2.8334 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 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 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 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 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 2 0 35 37 1 0 33 38 1 0 38 39 2 0 38 40 1 0 20 41 1 0 19 42 1 0 15 43 1 0 11 44 1 0 4 45 1 0 43 12 1 0 42 16 1 0 40 31 1 0 1 46 1 0 1 47 1 0 1 48 1 0 2 49 1 0 2 50 1 0 3 51 1 0 3 52 1 0 4 53 1 0 5 54 1 0 5 55 1 0 6 56 1 0 6 57 1 0 7 58 1 0 7 59 1 0 8 60 1 0 8 61 1 0 9 62 1 0 9 63 1 0 10 64 1 0 10 65 1 0 11 66 1 1 12 67 1 1 13 68 1 0 13 69 1 0 14 70 1 0 14 71 1 0 15 72 1 1 16 73 1 6 17 74 1 0 17 75 1 0 18 76 1 0 18 77 1 0 19 78 1 1 20 79 1 6 21 80 1 0 21 81 1 0 22 82 1 0 22 83 1 0 23 84 1 0 23 85 1 0 24 86 1 0 24 87 1 0 25 88 1 0 25 89 1 0 26 90 1 0 26 91 1 0 27 92 1 0 27 93 1 0 28 94 1 0 28 95 1 0 29 96 1 0 29 97 1 0 30 98 1 0 30 99 1 0 31100 1 0 32101 1 0 32102 1 0 33103 1 0 34104 1 0 34105 1 0 37106 1 0 37107 1 0 37108 1 0 41109 1 0 44110 1 0 45111 1 0 M END

Standard InCHIKey	NPGCUMNTYUYRCR-RWIDSCNISA-N
Standard InCHI	InChI=1S/C37H66O8/c1-3-16-29(39)17-12-10-11-15-20-32(41)34-22-24-36(45-34)35-23-21-33(44-35)31(40)19-14-9-7-5-4-6-8-13-18-30-26-28(25-27(2)38)37(42)43-30/h28-36,39-41H,3-26H2,1-2H3/t28?,29?,30?,31-,32+,33-,34-,35-,36-/m1/s1
SMILES	CCCC(CCCCCC[C@@H]([C@H]1CC[C@H]([C@H]2CC[C@H]([C@@H](CCCCCCCCCCC3CC(CC(=O)C)C(=O)O3)O)O2)O1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	638.48	Volume:	687.887 ? Van der Waals volume.
Dense:	0.928	LogP:	4.486 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.562 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.471 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	25.0	Rigid Bonds:	17.0
TPSA:	122.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.071	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.916	Fsp³:	0.946
MCE-18:	46.111 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.861	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.009 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.482	Promiscuous compounds:	0.284

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.207	MDCK Permeability:	-4.837
Pgp-inhibitor:	0.001	Pgp-substrate:	0.362
PAMPA:	0.077 ? 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):	0.302
20% Bioavailability (F20%):	0.725	30% Bioavailability (F30%):	0.966
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.958
Plasma Protein Binding (PPB):	93.921%	Volume Distribution (VD):	0.375
Fu:	5.23% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.152
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.05
BSEP inhibitor:	0.394

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.796	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.64	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.956
CYP3A4-inhibitor:	0.856	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.005
HLM stability:	0.01 ? 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):

4.975

Half-life (T1/2):

1.112

ADMET: Toxicity

hERG Blockers:	0.235	hERG Blockers (10um):	0.496
Human Hepatotoxicity (H-HT):	0.639	Drug-induced Liver Injury (DILI):	0.129
AMES Toxicity:	0.018	Rat Oral Acute Toxicity:	0.01
Maximum Recommended Daily Dose:	0.27	Skin Sensitization:	1.0
Carcinogencity:	0.061	Eye Corrosion:	0.297
Eye Irritation:	0.928	Respiratory Toxicity:	0.652
Drug-induced Neurotoxicity:	0.019	Ototoxicity:	0.715
Hematotoxicity:	0.097	Drug-induced Nephrotoxicity:	0.667
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.019
A549 Cytotoxicity:	0.101	Hek293 Cytotoxicity:	0.027
BCF:	1.286 ? 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:	4.97 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.192 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.437 ? 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
NPO26659	Annona bullata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2778448]
NPO26659	Annona bullata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8350089]
NPO26659	Annona bullata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26659	Annona bullata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26659	Annona bullata	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26659	Annona bullata	Species	Annonaceae	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
ED50	3

Activity Type	# Activity
Cell line	3

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
NPT81	Cell line	A549	Homo sapiens	ED50	=	3.29	10'-11 ug/ml	PMID[8350089]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	7.63	10'-4 ug/ml	PMID[8350089]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	1.09	10'-12 ug/ml	PMID[8350089]

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
-	Artemia	LC50	=	0.158	ug.mL-1	PMID[8350089]

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 NPC480076 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	15544
0.1-0.2	31932
0.2-0.3	2068
0.3-0.4	99
0.4-0.5	121
0.5-0.6	50
0.6-0.7	3
0.7-0.8	0
0.8-0.85	4
0.85-0.9	6
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9583	High Similarity	NPC480077
0.9149	High Similarity	NPC480078
0.9149	High Similarity	NPC480071
0.898	High Similarity	NPC480075
0.875	High Similarity	NPC482767
0.875	High Similarity	NPC475260
0.875	High Similarity	NPC488621
0.875	High Similarity	NPC473775
0.875	High Similarity	NPC488622
0.84	Intermediate Similarity	NPC480251
0.84	Intermediate Similarity	NPC480250
0.8125	Intermediate Similarity	NPC474100
0.8125	Intermediate Similarity	NPC475232
0.7818	Intermediate Similarity	NPC473791
0.75	Intermediate Similarity	NPC475616
0.7451	Intermediate Similarity	NPC488234
0.7358	Intermediate Similarity	NPC473699
0.7358	Intermediate Similarity	NPC51249
0.6863	Remote Similarity	NPC480072
0.65	Remote Similarity	NPC475206
0.6154	Remote Similarity	NPC480074
0.5833	Remote Similarity	NPC169511
0.5833	Remote Similarity	NPC287164
0.5833	Remote Similarity	NPC234077
0.5789	Remote Similarity	NPC93794
0.5789	Remote Similarity	NPC473504
0.5789	Remote Similarity	NPC81778
0.5789	Remote Similarity	NPC40066
0.5614	Remote Similarity	NPC81045
0.5614	Remote Similarity	NPC39754
0.5614	Remote Similarity	NPC171135
0.5614	Remote Similarity	NPC61257
0.5614	Remote Similarity	NPC320569
0.5614	Remote Similarity	NPC133730
0.5614	Remote Similarity	NPC191929
0.5614	Remote Similarity	NPC100454
0.5614	Remote Similarity	NPC242364
0.5614	Remote Similarity	NPC172821
0.5614	Remote Similarity	NPC274446
0.5614	Remote Similarity	NPC485251
0.5614	Remote Similarity	NPC151403
0.5614	Remote Similarity	NPC261952
0.5614	Remote Similarity	NPC605171
0.5593	Remote Similarity	NPC42598
0.5593	Remote Similarity	NPC485252
0.5556	Remote Similarity	NPC91067
0.5517	Remote Similarity	NPC473649
0.5517	Remote Similarity	NPC473156
0.5517	Remote Similarity	NPC154097
0.5517	Remote Similarity	NPC159750
0.5517	Remote Similarity	NPC73248
0.5517	Remote Similarity	NPC282815
0.5517	Remote Similarity	NPC470401
0.5517	Remote Similarity	NPC600956
0.5517	Remote Similarity	NPC610454
0.55	Remote Similarity	NPC602738
0.5424	Remote Similarity	NPC473671
0.5424	Remote Similarity	NPC475268
0.5424	Remote Similarity	NPC470400
0.5424	Remote Similarity	NPC77871
0.5424	Remote Similarity	NPC9678
0.5424	Remote Similarity	NPC319036
0.5424	Remote Similarity	NPC604764
0.5424	Remote Similarity	NPC605867
0.5385	Remote Similarity	NPC473663
0.5385	Remote Similarity	NPC473723
0.5385	Remote Similarity	NPC475173
0.5357	Remote Similarity	NPC228411
0.5333	Remote Similarity	NPC132940
0.5246	Remote Similarity	NPC20533
0.5079	Remote Similarity	NPC473995

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC480076 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5905
0.1-0.2	3166
0.2-0.3	79
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